BE101

Ja

molar flux (number of moles per unit time per unit area) of solute A

CAm

molar concentration of A in membrane phase (molm^-3)

DAm

diffusion coefficient for solute A in membrane phase (ms^-1)

x

distance in x direction across the membrane phase

PAm

permeability of membrane for solute A (ms^-1)

C1 or C2

molar concentration of solute A in fluid 1 or 2, molm^-3

Jv

fluid volume flux, m^3m^-2s^-1

Lp

membrane hydraulic coefficient m^3m^-2s^-1Pa^-1

delta P

hydrostatic pressure difference across membrane, Pa

delta pi

osmotic difference across membrane, Pa

sigma

Staverman reflection coefficient

in what directions do blood and dialysate flow?

Counter current flow to one another

properties of the membrane

semi permeable, hydrophilic (cellulosic or polysulphone)

How is patient blood access taken in acute renal failure cases?

cannulation of subclavian vein with double lumen

How is patient blood access taken in end stage renal failure cases?

operation done to connect venous and arterial blood supply in arm to provide an arterio-venous fistula

How does an arterio-venous fistula work?

Over time, the vein becomes arterialised allowing safe cannulation. Cannulation of AV fistula at two points (blood to and from dialyser)

typical haemodialyser membrane area

0.8 to 1.4m^2

blood flow rate

150 to 350 ml/min

dialysate flow rate

500 to 800 ml/min

ultrafiltrate rate

3 to 5 ml/min

haemodialyser design requirements

efficiency in removal of waste, solutes and water, small internal blood volume, minimal blood retention after use, low to moderate resistance to blood flow and must be safe and easy to use, sterile and cheap

what are the two main geometries of dialyser used?

parallel plate and hollow tube. Most dialysers in current use are hollow tube

Why are all device units supplied as a single use disposable sterile unit?

reduced set up time and reduced chance of infection

How is a large membrane area achieved in parallel plate?

multiple folded plates and membranes are stacked

how do parallel plate designs work?

blood passes between two sheets of membrane. The membranes are supported by grooved plastic plates. Dialysate flow is in the opposite direction to blood flow

describe the design of hollow fibre dialysers

5 to 20000 fine bore (200 micrometres) membrane tubes (hollow fibres), the ends of which are embedded in potting resin and the bundle encased in a plastic shell. Entry and exit points in the plastic shell allow dialysate fluid to be pumped around the outside surface of the hollow fibres

Mass transfer performance - clinical approach

dialyser = black box, use molar concs and apply conservation of mass of solute to blood compartment

Efficiency =

clearance/rate at which solute enters

why is efficiency higher for smaller molecules (eg urea, mw 60) than larger molecules (eg vit B12, mw 1355)?

membrane is partially permeable so smaller molecules are more able to diffuse across from the blood into the dialysate

what does flow limited cases apply for?

small solutes and low Qb. exp(-KoS/Qb)=0 and Cl=Qb

where do membrane limited cases apply

large solutes and high Qb, Cl=PmS

what parameters is the removal of solutes by dialysis controlled by?

dialyser clearance and rate of solute transfer between body fluid compartments

Single pool model for urea transfer

used as the basis for dialysis treatment planning

solute mass balance on the pool in general system

output=input + generation - consumption -accumulation

Why is the constant pool volume method commonly used?

ultrafiltration volume is low with respect to total pool volume

what is disequilibrium syndrome?

feelings of nausea and headache caused by the increase of osmotic pressure within the CSF space due to the slower release of urea from the cerebrospinal fluid into the main pool

how can disequilibrium syndrome by avoided/minimised?

less aggressive treatment regime, minimising difference in solute concentration between the main compartments and the CSF

for 3 dialysis sessions a week and daily protein intake 0.8 to 1.2g/kg body weight, what is the ratio of c(t)/c*

0.4

What should Clt/V be approximately equal to?

1

how can weight be converted to volume (L)?

body weight (kg) x 0.6

why has use of haemodialysis increased?

Ageing population with increasing wealth in the developed world, dialysis technology has improved, threshold for CRF has lowered. Type ii diabetes has increased, and diabetic nephropathy is the most common cause of CRF, and more people with CVD are surviving

What can haemodialysis costs be broken down into?

supplies, equipment, staff, transportation, labs, professionals

what is peritoneal dialysis?

PD uses the peritoneum as a membrane to provide treatment similar to HD. A dialysate solution (containing glucose) is infused into
the abdominal cavity, with solute transfer into this fluid occurring across the membrane.

advantages of peritoneal dialysis

simplicity, easy to use, portable, patient is in control

disadvantages of PD

Sterile solution exchanges necessary, takes up space, limited efficiency of peritoneum for some solute removal, peritonitis (significant hazard)

why is PD generally cheaper than HD?

reduced fixed costs, reduced medication costs, no external blood loss so no EPO, iron etc supplements required and less blood thinning drug therapy required

why are hospital admission costs for HD and PD similar?

peritonitis and fluid management issues

What function of the kidney cannot be directly replaced by a haemodialyser?

control of blood pressure

What is the main function of the glomerulus?

to act as a filter to remove excess water and solutes from the blood

True or false? Each kidney has a single Glomerulus, which is connected to the ureter via a tubule
structure.

false. There are millions of nephrons per kidney and hence millions of glomeruli

True or false? Each of the nephron units, which make up most of the kidney structure, consist of a Bowman’s capsule, a proximal tubule, a distal tubule, a loop of Henle and a
collecting tubule

true

true or false? Blood is delivered to and from the kidney by branches of the hepatic artery and vein respectively

false. Blood is delivered to and from the kidney by branches of the renal artery and vein respectively

True or false? Acute renal failure occurs over a period of hours or days and is usually reversible

true

True or false? Chronic renal failure occurs over a period of several years

True.

true or false? Acute renal failure is reversible and is commonly treated by haemodialysis via an AV-fistula blood access site.

False. Acute renal failure is reversible but is commonly treated by haemodialysis via
cannulation of subclavian vein with double lumen

What two mass transfer processes does haemodialysis use?

dialysis and ultrafiltration

how can ultrafiltration rate be increased during dialysis?

increasing pressure of blood flow

Blood flow through a haemodialyser is counter current to the flow of dialysate. Why is this
advantageous?

The clearance can be increased by maintaining a concentration difference between the blood and dialysate along the length of the dialyser

What is the most commonly used geometry and configuration for a haemodialyser?

Hollow-fibre with blood flow inside the fibres

If the Rm / Ro ratio for urea is 0.5 and the same ratio for vitamin B12 is 0.8, what can we say about the removal of these two molecules during haemodialysis? You can assume that the two molecules are not present in the incoming dialysate solution and their starting
concentrations in the blood are the same.

Rate of removal of urea will be greater than vitamin B12

Why is there a high rate of coronary heart disease in Glasgow?

weather (reduced vitamin D), diet, genetics, low income leading to increased stress and hypertension

properties of endothelial cells

permeability, thromboresistance, vascular tone, inflammatory and immune regulation

Smooth muscle cells are found in the media layer of arteries. What are their properties?

contractility, structural integrity, remodelling, metabolism

fibroblasts are found in the outer adventitia layer of arteries. What are their properties?

mechanical, vasa vasorum (vascularised), remodelling

What does the elastic lamina consist of?

extracellular matrix, collagen, elastin

performance of synthetic blood vessels

high failure rate, low patency (lumen doesn't stay open long enough), can lead to thrombosis and intimal hyperplasia, no coronary vessels

performance of synthetic blood vessels >10mm

used for life saving treatment of aortic aneurysm and other diseases of large blood vessels

issues with synthetic blood vessels

mechanical properties can't be replicated, compliance mismatch, hypertension and graft infection

examples of scaffolds

synthetic/natural polymers, hydrogels, surface functionalisation, bioactive, decellularised (from human or animal eg pig)

what needs to be considered when seeding a scaffold with cells?

cell type, source and how to isolate them, cell density, ECM composition and a functional assessment

biochemical properties for bioreactor

mass transport of nutrients and waste, control of pCO2, pO2 and pH

physical properties for bioreactor

temperature, acoustic, photodynamic, electromagnetic

biomechanical properties of bioreactor

flow rate, shear stress, pulse pressure/frequency, resistance, wall motion (compliance)

what is alginate?

widely used in biomedical applications due to its biocompatibility, low toxicity, good printability, ease of mechanical and physical properties, tunability and relatively low cost

Why do we need artificial grafts?

cell seeded grafts have longer development times limiting their potential applications

disadvantage of polyester grafts

they don't expand during systole like an artery would as arteries have specific microstructure and chemical composition

Why is making tissue engineered grafts challenging?

Tissue engineered grafts are made up of millions of cells which are difficult to obtain and then keep alive and healthy while remaining as the desired cell type

What type of printing is used to create anatomically accurate arteries?

FRESH printing

How is cardiovascular disease treated using engineering?

coronary artery bypass graft or angioplasty

Why aren't stents affected by the immune response?

the metal cage is coated in chemotherapy drugs which last around 2 months until the artery stabilises. This prevents cell proliferation

Advantages of a biodegradable stent over stainless steel stents

the stent will eventually break down and the artery will remain open

Why aren't biodegradable stents used?

Biodegradable stents cost around £2000 to produce whereas traditional stents cost around £100. Biodegradable stents will therefore only be used by healthcare providers if proven to give better results

Diagnostic for a required coronary artery bypass graft

blood test to check for elevated troponin levels

Who is CABG recommended for?

people with multi vessel disease and some patients with complex lesions and/or comorbidities

flowrate of cardiopulmonary bypass

3 to 6 litres per minute

materials used for oxygenator membrane

homogeneous (silicone rubber), microporous or a mixture of polyurethane and polyethylene

describe balloon angioplasty

the radial artery is cannulated to deliver a balloon to vessel blockage site, the balloon then expands to open the artery and restore blood flow

How does a multidisciplinary team reduce amputation rates?

reduction of peak pressures, infection treatment, regular debridement (removal of dead/infected tissue) and restoring arterial perfusion

responsibility as orthotists when dealing with the diabetic foot

pressure relief

low risk diabetic foot patients

no risk factors present eg no loss of sensation, no peripheral arterial disease

treating low risk diabetic foot patients

Annual screening by trained professional to determine personal footcare and self care plan. Review footwear and educate on accessing podiatry and cardiovascular risk reduction

moderate risk diabetic foot patients

one risk factor present such as loss of sensation, sign(s) of peripheral arterial disease, unable to self care, eGFR less than or equal to 15

treating moderate risk of diabetic foot

same as low risk patients as well as further foot assessment and treatment/management plan by podiatrist and considering provision of specialist footwear. Measurements and fittings by orthotist/podiatrist may be carried out

high risk of/ in remission diabetic foot patient

either previous ulceration/amputation /consolidated charcot (weakening of bones and soft tissues of the foot or ankle) or more than one risk factor

treating high risk/remission diabetic foot patients

assessment by podiatrist with diabetic foot experience, referral to other required specialists, further review of patient's normal/prescription footwear and insoles, especially if in remission

patients with active diabetic foot

active ulceration/infection, with or without ischaemia, gangrene or unexplained hot red swollen foot with/without pain

treatment of active diabetic foot patients

same as high risk/remission patients as well as rapid referral and management to a member of multidisciplinary diabetic foot team or directly to vascular

intrinsic risk factors to diabetic foot

neuropathy, peripheral artery disease, structural deformity, hyperkeratosis, amputation, limited joint mobility, age/weight, visual impairment, previous ulceration

extrinsic risk factors to diabetic foot

minor trauma, footwear eg seams leading to damage, thermal injury, chemical burns, bathroom (at home) surgery, occupational hazards, poor diabetic knowledge, living alone

What is neuropathy?

loss of feeling in extremities (hands and feet)