Renal - Week 3 Flashcards
describe acid production in the body
• Cellular respiration
o Produces CO2 which reacts with water to form carbonic acid
• Metabolic processes
o Give rise to non-volatile acids: ketones, lactate etc
o ~60 mmol non-volatile acids per day
o In 14L this would make the body pH 2.3
describe how acid homeostasis is maintained
• Buffers (rapid)
o Bind to protons to reduce acidity
o Proteins e.g. Hb
o Bicarbonate
• Lungs (fast)
o Remove CO2
o Limited by HCO3 reserves
• Kidneys (slow)
o Excrete H into urine
o Recover HCO3
what happens in hypoventilation
- Increased CO2 respiratory acidosis
- Lung disease, airway obstruction, neurological problem leading to depressed breathing such as head injury or opiate overdose
what happens in hyperventilation
- Less CO2 respiratory alkalosis
* Panic attack in response to pain or asthma
how can you get metabolic acidosis
• Increased protons
o Over production of acid such as lactic acidosis (tissue hypoxia) or ketoacidosis (diabetes, starvation, alcohol)
o Impaired excretion
Acute kidney injury or CKD
• Losing bicarbonate
o Severe diarrhoea
o Fistula formation in small bowel
o renal tubular acidosis type II
how can you get metabolic alkalosis
• Unusual loss of protons o Vomiting o Severe hyperkalaemia o Hyperaldosteronism • Unusual ingestion of bicarbonate
what are the compensation mechanisms for each acid base disturbance
metabolic acidosis
- increased RR to lower CO2
- increased renal recovery of HCO3
metabolic alkalosis
- decreased RR to increase CO2
- decreased renal recovery of HCO3
- usually marginal
respiratory acidosis
- increased renal recovery of HCO3
respiratory alkalosis
- decreased renal recovery of HCO3
- usually marginal
how is HCO3 calculated
using the henderson-hasselbalch equation
CO2 + H2O H2CO3 H + HCO3
what is important to remember about arterial blood gases
Blood gases often performed on the radial artery – can damage artery
Need to be analysed asap and not sent by pneumatic tube – pressure
We only need H, pO2, pCO2 and HCO3
Base excess and HCO3 are calculated by the analyser
Base excess is the amount of H per L of blood, required to return the pH to reference range at pCO2 of 5.3kPa
Should only be deranged where a metabolic disorder is present
describe standardised bicarbonate
- What the HCO3 conc would be if pCO2 were reference range (5.3kPa)
- Std bicarb should only be deranged where a metabolic disorder is present
- Purely metabolic disorder - approx. equivalent to actual bicarb
- Mixed resp-meta disorder - significant difference to actual bicarb
what are the effects of metabolic acidosis
• Cardiovascular
o Negative inotropic effect (if severe)
• Oxygen delivery
o Acutely – H causes R-shift of oxyHb dissociation curve (facilitates oxygen delivery)
o After several hours – H reduces 2,3-DPG causing L-shift of curve (impairs O2 delivery)
• Nervous system
o Impaired consciousness
• Potassium homeostasis
o H leakage from cells causing high plasma K, may also be lost renally
o If above sustained, total body K can be depleted
• Bone
o If chronic, acidosis can get buffered by bone
o Leads to decalcification
describe the relationship between metabolic acidosis and anion gap
some causes have anion gap and some done
elevated o DKA o lactic acidosis o salicylate overdose o ethylene glycol, methanol poisoning o renal failure
normal
o severe diarrhoea
o high intestinal fitula output
o renal tubular acidosis
what are the effects of respiratory acidosis
hypercapnia -
o shortness of breath
o neurological - anxiety, coma, headache, myoclonus
o systemic vasodilation
o hypoxia
what are the effects of metabolic alkalosis
not usually significant
K moves into cells
beware effect of IV bicarbonate in CKD as metabolic acidosis is common in CKD - acute fall in acidity can reduce solubility of calcium salts and increase risk of systemic calcification
Remember the compensation for alkalosis is limited
what are the effects of respiratory alkalosis
acute hypocapnia
o cerebral vasoconstriction - light headedness, fits, confusion, syncope
o fall in ionised calcium -perioral, peripheral parasthesia
cardiovascular
o increased heart rate
o vasoconstriction - possible angina in those with coronary artery disease
Remember the compensation for alkalosis is limited
how can you get respiratory acidosis
acute o airway obstruction o cardio-resp arrest o infective exacerbation of COPD o pneumonia o neurological - opiate toxicity, guilllain barre syndrome, myasthenia gravis
chronic o COPD o obstructive - obesity o restrictive - pulmonary fibrosis o neurological - MND, myopathy
how can you get respiratory alkalosis
usually acute in nature o asthma, COPD. PE o pain, panic attack o iatrogenic o altitude sickness
o inappropriate stimulation of respiratory centre
• head injury
• raised ICP
• local tumour
• metabolic e.g. hepatic encephalopathy, poisoning
chronic
o pregnancy - mild resp alkalosis compensated by minor metabolic acidosis
what are the immune systems normal functions?
Recognition of ‘non-self’or ‘abnormal self’
Protection from pathogens (bacteria, viruses etc)
Surveillance for tumours
what are the components of the immune system
Innate immune system
Macrophages
Neutrophils
Complement & natural antibodies (IgM)
Adaptive immune system
Dendritic cells (antigen presentation) T cells (helper and cytotoxic T cells) Natural Killer (NK) cells - cytotoxic B cells (antibody generation & memory)
describe MHC (Major Histocompatibility Complex)
MHC in humans called Histocompatibility Locus Antigen (HLA)
These molecules imprint ‘individuality’ on cells and are pivotal in the generation of immune responses
HLA genes are very polymorphic i.e. there are many different variations possible at each gene locus
Class I molecules: HLA-A, -B and -C
Expressed by most somatic cells of body
Used to present peptides from internally processed proteins
Class II: HLA-DP, -DQ and –DR
Expressed by Antigen Presenting Cells (DCs etc) that constantly ’sample’ their microenvironment
Used to present antigenic peptides derived from digested material (including pathogens, abnormal or foreign cells)
Class I: HLA-A, -B and -C
If Class 1 HLA molecule is associated with virus-derived protein then the cell is recognised as infected
Infected cell will be killed by cytotoxic T cells
Class II: HLA-DP, -DQ and –DR
Used by Antigen Presenting Cells (DCs etc) to present antigenic peptides derived from digested and processed material
Cell surface expression of a peptide derived from a pathogen or foreign cell will stimulate a T cell immune response
what are the key principles of transplant immunology
Rejection of Tx is directed at specific proteins called antigens
Rejection is donor specific
Rejection may be both Cell or Antibody mediated
Rejection exhibits ‘memory’ i.e. a 2nd similar Tx is rejected MORE RAPIDLY and this results from the rapid generation of cytotoxic antibodies that recognise the Tx
describe HLA profiling
Performed using molecular biological and serological techniques
e.g. HLA-A1 and A3,
HLA-B44 and B44
HLA-DR7 and DR15
The HLA tissue types of all patients on the Kidney Transplant waiting list is held on a central UK database and the ‘best match’ chosen when kidneys become available
Used to allocate kidneys but less important for other organs such as liver (less immunogenic)
If all HLA-A, -B and –DR loci are the same the it is a 0-0-0 mismatch
If they are all different then it is a 2-2-2 mismatch
describe immunosuppressive treatment
Corticosteroids
Kill lymphocytes
Interfere with T cell activation and gene transcription
Powerful anti-inflammatory agents
Calcineurin inhibitors (CNI) – Tacrolimus Inhibit T cell activation by interfering with intracellular signaling pathways
Anti-proliferative agents - mycophenolate mofetil (MMF)
Inhibit clonal expansion of T cells
Various monoclonal and polyclonal antibodies directed against:
IL-2 receptor blockers (IL-2 stimulates clonal expansion of T cells)
T cells (cytotoxic complement fixing Abs)
Co-stimulatory molecules
which organs are transplantable
Kidney Pancreas (complete organ or pancreatic islets) Liver Lung Heart Small Bowel Cornea Faces, arms etc
what needs to be assessed in patients needing a transplant
Age important (biological vs chronological!) - frailty
Primary cause of renal failure e.g. polycystic kidneys versus conditions which can recur in a Tx (e.g. aHUS, FSGS)
Comorbid disease e.g. cardiovascular disease (IHD, PVD), diabetes etc
History of infections
History of tumours (need tumour free period)
Urological disease e.g. bladder dysfunction
Additional investigations:
CARDIAC - exercise ECG, myocardial perfusion studies
Angiography (need decent vessels for the anastomosis)
Urodynamic studies
Tumour markers, imaging etc
what are the types of transplant?
Cadaveric Tx (commonest) e.g. subarachnoid haemorrhage • DCD = donated after cardiac death • DBD = donation after brain death Living related donor Tx • Sibling, spouse, altruistic Typically a kidney Tx
Live donation lasts longer than cadaveric
what are the criteria for a kidney Tx to go ahead?
Blood group (ABO) compatible (RIE now has an ABO incompatible programme)
Immunological ‘X-match negative’
• Take serum from the recipient and donor lymphocytes
• Add a complement e.g. vital dye which will enter killed cells and turn them a colour if they are matched to recipient antibodies
describe anti-HLA antibodies
If a person is exposed to a foreign HLA molecule, they can produce an HLA antibody against this e.g. patient is A1, A24 and with exposure to A31 generating an anti-A31 antibody
Approximately 30% patients on renal waiting list have anti-HLA antibodies
The ‘specificity’ of these antibodies has to be defined (e.g. A31, B8, DR3 etc)
Highly sensitised patients exhibit high levels of cytotoxic Abs to many HLA antigens that may be derived from:
• Previous transfusions (WBC filtered)
• Pregnancies
• Previous Transplantation
