Week 4 Flashcards
What important points does The Equality Act 2010 impact on?
Fairness of access
Employers responsibility in discrimination against patients by members of staff and vice versa
Discrimination by employers against staff
Define diversity
Acknowledgement of alterity among people
Define equality
Fairness of opportunity and observing the rights of people so that their alterity is not discriminated against
Define equity
Treating equals equally and unequals unequally
What is the difference principle?
Justice necessitates that inequalities in society are met with asymmetrical measures in the form of counter-inequalities
so as to achieve equity
What are the levels in Allport’s scale of prejudice?
Anti-locution, avoidance, discrimination, violence, murder
What diversity strands are protected by The Equality Act 2010?
Age, disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, race and ethnicity, religion and belief, sex, sexual orientation
What 3 conditions are always termed a disability?
Cancer, HIV infection, MS
Define disability
Physical or mental impairment which has a substantial and long-term adverse effect on the ability to carry out normal daily activities
What categories of discrimination are there?
Direct, indirect, associative, perceived, harassment, victimisation, instruction
What are the functions of the kidney?
Metabolic waste excretion Control of solutes and fluid Endocrine EPO regulation BP control Drug metabolism/excretion Acid-base balance
What is the normal percentage fluid distribution?
Intracellular - 63% (25L)
Extracellular - interstitial 30% (12L); intravascular 7% (3L)
Which component of extracellular fluid do the kidneys have control of?
Intravascular
What factors affect the afferent arteriole?
Sympathetic nervous system - vasoconstriction
Prostaglandins - vasodilation
What factors affect the efferent arteriole?
Angiotensin II - vasoconstriction
What percentage of filtrate is reabsorbed?
99%
What percentage of reabsorption occurs in the PCT?
70%
Outline the mechanism of the countercurrent multiplier
Thick ascending limb is impermeable to water but actively transports Na/K/Cl
Thick ascending limb provides a concentration gradient in the interstitium which promotes water reabsorption from the thin descending limb
Thin descending limb is freely permeable to salt and water
Vasa recta do not wash away the gradient due to countercurrent exchange
What is the mechanism of action of aldosterone and what drugs are used to block its actions?
Aldosterone produced in the zona glomerulosa of the adrenal cortex in response to angiotensin II/high K+ → epithelial Na channel insertion in CD → Na reabsorption and K loss
Spironolactone and amiloride
What information do urinary electrolytes give?
Rare to request - collected over 24 hours Na - induced natriuresis Cl - diuretic abuse Ca - differentiate Bartter's/Gitelman's K/urea - rarely used
What is the minimum and maximum daily urine output?
Minimum - 0.4 L/day
Maximum - 12 L/day
What is a syngeneic transplant?
Donor and recipient are genetically identical twins
What is an allogeneic transplant?
Donor and recipient are not genetically identical but are from the same species
What is a xenogenic transplant?
Donor and recipient are from different species
What tissues/organs can be donated from living donors?
Haematopoietic stem cells
Kidney
Liver lobe
Lung lobe
What tissues/organs can be donated from deceased donors?
Kidney Liver Pancreas Heart Lung Cornea
Who decides how transplants are allocated?
NHS Blood and Transplant directorate ensure organs are matched and allocated in an unbiased way
Takes into account clinical need, waiting time and compatibility
What antigen, antibody and donor compatibility does a patient with blood type A have?
Antigen - A
Antibody - anti-B
Donors - A, O
What antigen, antibody and donor compatibility does a patient with blood type B have?
Antigen - B
Antibody - anti-A
Donors - B, O
What antigen, antibody and donor compatibility does a patient with blood type AB have?
Antigen - A, B
Antibody - /
Donors - O, A, B, AB
What antigen, antibody and donor compatibility does a patient with blood type O have?
Antigen - /
Antibody - anti-A, anti-B
Donors - O
What is the consequence of blood group incompatibility?
Hyperacute rejection of transplanted organ immediately after connection of blood vessels
May be overcome by immunoadsorption/plasma exchange/immunosuppression
What is the major histocompatibility complex?
Group of genes on chromosome 6 associated with the acceptance and rejection of transplanted material from genetically different donors
What are the HLA classes?
Class I - HLA-A, HLA-B, HLA-C
Class II - HLA-DR, HLA-DQ, HLA-DP
What is the structure of HLA genes?
Single polypeptide chain associated with β2 microglobulin
Polymorphisms at exons 2 and 3 encode α1 and α2 domains which are most distal and responsible for the function of the HLA molecule
Cleft of HLA binds peptides from degradation of cellular proteins which signals T cells
How do class I HLA present protein to CD8 T cells?
- Peptides formed by proteolytic degradation
- Peptides transported by TAP from the cytoplasm to ER
- MHC associates with TAP accessory molecules (tapasin)
- Assembled MHC transported via Golgi to cell surface to interact with CD8+ T-cells (normal peptide = no response; abnormal peptide = immune response)
Intracellular proteins
How do class I HLA present protein to CD4 T cells?
- Proteins assembled partially in ER; α and β chains join in association with the invariant chain polypeptide (stabilises and stops peptide binding in the ER)
- HLA transported via Golgi to vesicles where HLA-DM aids association of antigenic peptides to the molecule
- HLA protein is transported to the cell surface when an optimum peptide has bound to the binding groove so it can interact with CD4+ T-cells
Extracellular and cell surface proteins
What cells do class I MHC molecules present to?
CD8 T cells
What cells do class II MHC molecules present to?
CD4 T cells
Where are class I and class 2 molecules expressed?
Class I - all cells and platelets
Class II - APCs, activated T cells, distressed cells
What is the main advantage and disadvantage of HLA polymorphism?
Increase chances of human survival
Makes transplantation more difficult
How is HLA matching used for kidney, liver and cardiothoracic transplants?
Kidney - match A, B and DR; avoid transplant in presence of donor-specific antibody
Liver - not matched; immunoprotected
Cardiothoracic - HLA matching important but not logistical due to time constraints; avoid transplant in presence of donor-specific antibody
Immunosuppression used in all of the above
How can patients posses antibodies against non-self HLAs and what does this mean for transplantation?
Pregnancy, blood transfusion, previous transplant, cross-reactivity of viral infection
Contraindication to transplantation if these antibodies match the donor
What is hyperacute rejection?
Rejection of a transplant within minutes-hours
Should not happen as patients are monitored, cross-matching occurs and antibodies are checked
Extremely rare
Complement activation, inflammation and thrombosis
What is acute rejection?
Rejection of a transplant within weeks-months
Immune mediated (T-cells (cellular) and B-cells (antibodies))
Treated with modulation of immunosuppression
Risk factor for chronic allograft nephropathy
What is chronic allograft nephropathy?
Rejection within months-years
Occurs in all transplants eventually
Painless but progressive form of primarily immunological injury to graft, more slowly compromises organ function than acute rejection
Influenced by immunological and non-immunological
How are kidney transplants from heart-beating donors allocated?
National scheme
Priority to 3, 4 and 5 according to points score based on waiting time, HLA match, age difference, location and blood group match
1. Paediatric patients (HLA match), highly sensitised (priority given based on waiting time)
2. Other Paediatric patients (HLA match) (priority given based on waiting time)
3. Adult patients (HLA match), highly sensitised
4. Other adult patients (HLA match and favourable m/m)
5. All other eligible patients
What tests are important to perform prior to transplantation?
HLA typing of the patient and donor
Patient screening for pre-formed HLA antibodies
Cross-matching of patient and donor to ensure no negative reaction
What is the function of the bladder?
Store urine at a low pressure without much sensation
Empty fully at a socially convenient time
Allow reciprocal contraction and relaxation of bladder and urethra
What is the normal capacity of the bladder?
400-500 ml
What ligaments hold the neck of the bladder in place?
Puboprostatic/pubovesical ligaments
What ligament is attached to the superior surface of the bladder?
Median umbilical ligament
How many layers does the detrussor muscle have?
3 - longitudinal, circular, spiral
What is the trigone of the bladder?
Smooth triangular area where the ureteric orifices are
What sphincters are present in the bladder/urethra?
Smooth muscle at bladder neck
Intra-mural striated muscle (rhabdosphincter) with small slow twitch fibres - along length of urethra in women and at the base of the penis in men
Peri-urethral striated muscle (pelvic floor) with larger fast and slow twitch fibres - just before urethral opening in women and at the base of the penis in men
What factors contribute to urethral closure?
Muscular occlusion by rhabdosphincter
Transmission of abdominal pressure to proximal urethra
Mucosal surface tension
Anatomical configuration at bladder neck
Submucosal vascular plexus
Inherent elasticity
Urethral length
What arteries supply the bladder?
Superior and inferior vesical arteries (branches of internal iliac artery)
What is the venous and lymphatic drainage of the bladder?
Rich plexus of veins draining into the internal iliac vein
Lymphatics drain into vesical, external iliac, internal iliac and common iliac lymph nodes
What is the afferent innervation of the bladder?
Simple nerve endings - in lamina propria and detrussor ascend with parasympathetics to the pontine and micturation centres; sense bladder filling, stretch and pain (polymodal)
Sympathetic - hypogastric nerve; sense pain, touch and temperature
What is the efferent parasympathetic innervation of the bladder?
Sacral preganglionic parasympathetic nuclei in intermediolateral columns of S2/3/4 run with pelvic nerves via pelvic plexus to bladder wall - cholinergic excitatory input to detrusor
Noradrenergic terminals in pelvic ganglia - nerve mediated detrusor inhibiton
What is the efferent sympathetic innervation of the bladder?
Preganglionic sympathetic nerves from T10-12 and L1-2 travel in hypogastric nerve to innervate trigone, blood vessels and smooth muscle of prostate in men/sparse innervation of bladder neck and urethra in women
Some postganglionic sympathetic nerves terminate in ganglion - inhibitory, gating theory
What is gating theory?
Afferent input to SC is cancelled out by inhibitory interneurons, restricting transmission to preganglionic parasympathetic cell bodies
Postganglionic sympathetic nerves exert inhibitory effect in parasympathetic ganglia
Therefore postganglionin parasympathetic fibres are protected from afferent input until threshold is reached
How is the urethral sphincter innervated?
Dual innervation - preganglionic somatic fibres (striated muscle) and parasympathetic nerves from S2-4 (Onuf’s nucleus); run via perineal branch of pudendal nerve
What additional arteries supply the bladder in the female?
Vaginal and uterine arteries
