Case 6

Stroke and Renal - last case of stage 2

What is a stroke?

clinical syndrome of presumed vascular origin, characterised by rapidly developing signs of focal or global disterbance of cerebral functions, which last >24 hours or leads to death

What is a TIA?

Transient ischaemic attack is a transient (<24h) neurological dysfunction caused by focal brain, spinal cord or retinal ischaemia without evidence of acute infarction.

What are the types of strokes?

85% ischaemic and 15% haemorrhagic

What can strokes lead to?

risk of futher vascular event, neurological problems, depression and anxeity, communication difficulties and difficulties with activies of daily living

What are the signs of a stroke or TIA?

sudden onset of focal neurological symptoms, including numbness, weakness, slurred speech and/or visual disterbance that cannot be explained by another condition, weakness and numbness genrally occurs on one side of the body or in a specific area, spotting or narrowing od vision if that area of the brain is effected, with TIAs completed respolved symptoms in 24hs of onset, stroke when symptoms are ongoing or has persisted for longer than 24hs

What are TIAs known as by the public?

mini stroke

What is a large artery low-flow TIA (true TIA)?

obstructive vascular process in extra-cranial or intra-cranial arteries, short-lived (minutes) and often recurrent, may occur several times a year, symptoms due to ischaemia involve numbness of hand, leg, arm, face, tongue or cheek, can have triggers or out of the blue

What is an Embolic TIA?

embolus may arise from a pathologic process in an artery - usually extra-cranial and caused by AF or LV thrombus, lasts hours and may be infrequent

What is a lacunar or small penertrating vessel TIA?

transient cerebral ischaemia induced by stenosis of intracerebral penetrating vessels, seen less frequently

When do most TAs resolve within?

1 h

What are the focal neurological deficits with TIAs?

unilateral weakness or sensory loss, dysphasia, ataxia, vertigo, loss of balance, syncope, amaurosis fugax, diplopia, or homonymous hemianopia, cranial nerve defects

What is ataxia?

loss of body movements

What is syncope?

temporary loss of contiousness

What is amaurosis fugax?

sudden transient loss of vision in one eye

What is the condition which has similar symptoms to strokes?

hypoglucaemia

What are the clinical features of strokes?

vary depending on causitive mechanism and area of brain affected, confusion, altered level of consciousiness, coma, headache, unilateral weakness or paralysis in the face, arm or leg, sensory loss - paraethesia or numbness, ataxia, dysphasia, difficulty with fine motor coordination and gait, visual disturbance 0- homonymous hemianopia, diplopia, nausea, vomitting

Describe the type of headaches assocaiated with stroke?

intracranial haemorrage - insidious onset and gradually increasing intensity
subarachnoid haemorrhage - severe headache maybe associated with neak stiffness, sentinel headaches may occur in preceding weeks

What causes a Ischaemic stroke?

thrombotic - often as complication of atherosclerosis
embolic - an embolus of fatty material from an atherosclerotic plaque or a clot in the larger artery of the heart - often complication of AF or atherosclerosis of carteroid arteries
narrowing/weakening of blood vessels
leads to death of tissue

What causes a haemorrhagic stroke?

bleeding within brain, bleeding on surface of brain

What are the risk factors of a stroke?

previous stroke/TIA, previous MI, Hypertention, heart failure, AF, hyperlipidemia, increased age, diabetes, ischemic heart disease, smoking, alcohol and drug missue, physical inactivity, poor deit

What are the complications following stroke/TIA in the early period?

cerebral oedema, delirium, serizures, VTE, cardiac complications, infection

What are the long-term complications of a stroke/TIA?

mobility problems, sensory problems, continence problems, pain, fatigue, swallowing, hydration and nutrition, sexual dysfuction, skin problems, visual problems, cognitive problems, difficulties with activities of daily living, emotional and psycological problems, communication problems, skin problems, financial problems

What do you do immediately if you suspect acute stroke?

immediate emergancy admission for anyone with suspected acute stroke or emergent transient ischaemic attack, may have ongoing focal neurological defects with a negative fast test, ensure hospital gets advanced notice of arrive, give time of onset, symptom evolution, current condition, and meds, DO NOT START anticoagulation or antiplatelet treatment, until brain imaging, while awaiting transfer monitor and manage any deterioration in clinical condition, give supplimental O2 to people if Ox stats less then 95% unless counterindercated

What is the acute management of stroke>

ensure patient airway to avoid hypoxia, monitor blood glucose between 4-11mmol/L, monitor BP, urgent CT scan/MRI scan, thrombolysis consider, nil by mouth until swallow assessed, keep hydrated but don’t over hydrate as risk of cerebral oedema, explain what has happened - communicate fully with patient, relatives and carers, antiplatelet agents after haemorrhagic stroke excluded - asprin 300mg, admit to stroke unit

When do you consider giving thrombolysis with stroke?

if 18-80 years and onset of symptoms <4.5 h ago, all patients that recieve thrombolysis need CT head 24h-post tx to rule out intracranial haemorrhage

When and what follow ups should occur post-stroke?

6 months, than at least annually to reveiw health, social care needs, ongoing risk factors, and secondary prevention, arrange review of carers of people with stroke 6 months and then annually to assess health and social care needs

What secondary prevention information do you need to provide (not specific drugs)?

information about risk factors to them and their family, strok associated, advice about driving, advice about returning to work, verbal and written information about drugs including reasons for meds, how and when to take it, common adverse effects, monitorin

What medications are involved in secondary prevention of stroke?

antiplatelet therapy, lipid modification, anti-hypertensive, and anticoagulants

When is antiplatelet therapy given for strokes?

initiated by secondary care on diagnosis of ischemic stroke or TIA without paroxysmal or permanent AF for long term vascular prevention

What antiplatelet therapy is given post-stroke?

clopidogrel 75mg, asprin 75mg daily with modified-release dipyridamole 200mg twice daily if contraidercated or cannot be tolerated, may be used if both asprin and clopidogrel cannot be tolerated or counterindercated, asprin used if other two contraindicated, dual therapy with asprin and clopidogrel (for up to 90 days), or asprin plus ticagrelor (for 30 days) may be initiated in secondary care for some people, followed by antiplatelet monotherapy

What lipid modification is given in secondary prevention stroke management?

unless contraindercated treatment with a high-intensity statin - atorvasatin 80mg daily, will be offered at diagnosis

What is the aim of statin therapy?

reduce non-HDL cholesterol by more than 40%, this reduction is not acheived within 3 months, consider adherance, deit, lifestyle and increasing dose

What is the target of managing hypertention post-stroke?

systolic below 130mmHg (or 140-150mmHg in people with severe bilateral cartid artery stenosis

what are the cercumstances of when anticoagulant drugs are given?

for people with ischaemic stroke or TIA and paroxysmal, persistant or permanent atrial fibrillation or atrial flutter, once intrecranial bleeding excluded

When are anticoagulant drugs given?

treatment in people with TIA starts immediately once imaging has excluded haemorrhage
defered treatment for varible periods in people with non-disabling ischaemic stroke depending on specific circumstances but starts with 14 days of onset, treatment is deffered until at least 14 days from onset in people with disabling ischaemic stroke, asprin 300mg daily used in interim

What does DOAC stand for?

direct oral anticoagulant

Who should anticoagulation not be used for?

people with stroke or TIA in sinus rhythm unless other indications are present

What are the rules around driving after stroke?

one TIA - not drive for one month, multiple TIAs - not drive for 3 months and notify DVLA - driving resumes if no futher TIAs, one stroke - not drive for 1 month, may need to tell DVLA, resume after one month if satisfactory clinical recovery, DVLA don’t need to be told unless residual neurological deficit 1 month after episode and in particular any visual feild defects, cognative defects and impared limb function, eligibility for disabled concessions e.g. blue badge

What is the post-stroke advice about returning to work?

need for assement with the rehabilitation scheme?, reffered through job center to a specialist in employment for people with disability ot specialist vocational rehabilitation team if extra support or advice needed

What are the things that you need to think about when managing long-term complications post-stroke?

continence problems, swallowing, nutrition and hydration, communication, mood and wellbeing, cognative dysfunction, oral health, fatigue

What is the treatment and advice around continence problems?

depends on cause, timed toiletting, prompted voiding, bladder retraining, pelvic floor exercises, in some cases drug treatments, may need to treat UTIs, consipation issues, fibre in deit, fluid intake and exercise, reveiw meds, consider toiletting routines and laxitives

How do you manage fatigue post-stroke?

assess for mental and physical factors that may contribute: e.g. depression, anxiety, adverse effects of meds, and disterbance of sleep by pain or apnoea, treat any reversible cause or exacerbating factors, provide info, reasurance, and support, to identify personal triggers and indercators, and develop stratergies to anticiperate and manage it, including energy condervation statergies

How do you manage oral health post-stroke?

advise them to carry out mouth care at least 3 times a day, due to any tubes fitted could affect oral health, mouth care can be prescribed, it is brushing teeth, cleaning gums with toothpaste and/or chlorhexidine dental gel, stick with foam end that can be dipped into water just to keep the mouth lubricated, removing excess secreations and applying lip barm, if they have dentures put them in during the day, clean them regularly with toothbrus, toothpaste and/or chlorhexidine dental gel, regular check-ups and replacement dentures if ill-fitting, damaged or lost, if using chlorhexidine gel for more than 7 days at a time can stain the teeth.

How do you manage cognitive dysfunction post-stroke?

consider screening all people with stroke and TIA for cognative imparement with appropriate tool, ensure decisions made with or on behalf of people with stroke are in line with the mental capacity act 2005, done by expert, so normally just refferal

What do you need to think about in regards to mood and wellbeing around stroke?

consider depression in all people with stroke, if one mood disorder is identified, assess for others, if severe or persistant mood disorders discuss with stroke physician or refer to phychiatry or phychology, consider refering for individual behavoir therapy if they have aphasia and low mood, consider breif phychological interventions before meds, if using antidepressants, monitor for adverse effects and treat for at least 4 months from initial recovery, after 2-4 weeks if not improved look at adherance, dose change or drug change, phychosocial interventions and support groups

How do you manage communication problems post-stroke?

ensure they receibe necessary support from speach and language therapist, if persistant and effects social activities refer to groups for people with aphasia

How to manage nutrition post-stroke?

regularly monitor deitary intake and nutritional status, refer to deitician if not enough, dissus with or refer to stroke specialist if unable to swallow or unable to tolerate nasogastric tube feeding initiated in hospital, ensure people who have difficulty self-feeding have access to equipment and assistance if needed.

Feeding tubes?

unconfortable and have a risk of infection, two types: nasogastral tube and enteric tube

What is dysphagia?

effected swallowing due to brain thing, afects most acute stroke patients, improves within 2 weeks for most, the complications are aspiration pneumonia, choking, comprimised nutrition and dehydration, reduced QoL, increase thickness of liquid to help,

What are the medication options for people with swallowing difficulties?

crushing and dispensing medications - need to give advice around this as don’t want altered dose, also this would be off-licence prescribing, switching formulation, resources to support with meds changes, may have to use special which are expensive and not stocked everywhere

What must you do when proposing medication changes due to swallowing difficulties?

if a liquid state dose in gs and mls, if crushed and dispersed state amount of water to disperse in, normally 15-30mLs ans whether it has to be in water, if multiple meds being crushed should be prepared and provided sepporatly,, nurse or patient, suggested timeline for reveiw of swallowing so can swap back as soon as, routes of communication

What are the two different types of nephrons?

cortical and juxtamedullary nephrons

What does the afferent arteriole do?

brings stuff to the bowman’s capsule, blood vessels narrow up to this point which increases the pressure and helps to force molecules through the cell spaces of the bowman’s capsule

What does the efferent arteriole?

take substances that aren’t filtered away from the bowman’s capsule

What happens to the bits and bobs once they have passed through the cell spaces in the bowman’s capsule

they go into the bowman’s space and then the proximal tubule

What do the macula densa cells do?

detect NaCl via the Na+-K+-2Cl- cotransporter, if they detect high amounts of NaCl they expand the efferent arteriole and contracts the afferent arteriole changing the pressure, this changes the pressure so less fluid gets filtered, lowered eGFR, Furosermide blocks the NKCC2 transporter so the system thinks there is low NaCl so increases eGFR
they are on the side of the distal convoluted tubule so can sence the pressure, if high volumes of fluid are being filtered this causes higher pressure, so changes diameter of arterioles to reduce the pressure

how much blood is being filtered every minute in a healthy individual?

625mL/min into the afferent arteriole, 120mL/min are filtered into the bowman’s capsule, produces 2mL/min of urine

What size of molecules can fit throught the bowman’s capsule?

<40 kDa

What are the pressures effecting how molecules get into the bowman’s capsules?

hydrostatic pressure from blood exerting pressure on the walls of the capillaries, blood colloid osmotic pressure from proteins that can’t go through, hydrostatic pressure from pushing it through the membrane, glomerular hydrostatic pressure opperates in the opposite direction

What dose ACEi do?

dilate the efferent arteriole which transiently decreases GFR

What is used as a marker for Bowman’s capsule membrane integrety?

one of the first substances to leak through into the urine if damage has occured, it does also go up after excersize but only a small amount

How much is the urine concentrated by using creatine? how?

100 fold, 60 fold by volume reduction, active transport of creatine via OCT2 into the urine makes up the rest

What does OCT2 stand for?

organic cation transporter 2

What are the proximal tubule transporters that you need to know about? and what you need to know around them?

OATs - organic anion transporters, organic anions in exchange for dicarboxylic acid, OAT3 transports organic anions like ciprofloxacin and methotrexate on the basolateral membrane, OCT2 responsible for the reuptake of cations like creatinine on basolateral membrane, they are other tranporters on the basolateral and apical membranes, a lot of them actively transport substances into the urine

How can we use urine pharmacokinetic data to tell us something about the metabolism of a compound?

if you know the AUC of drug excreted in the urine and the AUC in the plasma, we know how much went in and how much came out unchanged, AUCtotal - AUC urine = amout metabolised, fe unchanged = AUCurine/ AUCplasma, fe unchanged is fraction elimination unchanged

Why are you worried about drugs which have a high fraction eliminated unchanged?

more sensitive to renal damage as GFR can change the half life (increases it), metabolites are then filtered, so need to think about metabolite half life as well

How is the concentration time relationship effected by half life?

tail off is a lot longer, plasma concentration can be sustained for quite a while, if add another dose will build up the plasma concentration of the drug and it will become toxic

How do you work out how quickly the drug is extacted by the organ? how do you work out how efficient the organ is at extracting?

organ clearance = Q x (Cin-Cout)/ Cin Q - flow rate mL/min, C - concentration, extraction ratio = Qx(Cin - Cout)/ QxCin the Q cancels out, extraction ratio doesn’t care about flow rate

Why can’t we calculate renal clearence?

slow test which involves giving the drug to the patient that could harm them

What is the ideal way to work out renal clearance? and why?

inulin or a radioactive substance or metal , not-metabolised, have little distrbution outside the blood, excreated passively, non-toxic, and not protein bound, use GFR= urine flow x urine con./ plasma conc., GFR=renal clearance, however too slow and expensive for clinical practice

What equation is used to estimate renal clearance?

cockcroft-gault equation, this assumes a single serum messurement represents the whole day, serum creatine is effected by deit and there are errors as you are avaraging everything

What are the problems with eGFR?

fails to account for natural variations due to diet, time of day and muscle mass, it is only an estimate, to inform doseing good approximation but creatinine is not passively excreated so the drug may be secreated in a different way, the relationship should change with every drug so may not be linear

How do you classify renal disease in terms of GFR?

<10 is kidney failure, 10-30 is severe, 30-60 is moderate, 60-90 is mild, >90 is typical

How is renal related to cardiac?

kidney’s recive a ¼ of cardiac output, cardiorenal syndrome, if heart failure occurs can effect the kidneys

What is the function of the kidneys?

maintain constancy in the interor environment of the body

What do the kidney’s do?

filter blood to remove waste products of metabolism and toxins (elimination), regulate extracellular electrolyte, water and pH given varying environmental and dietary demands, secrete several essential hormones

What forces are applied at the glomerlous?

hydrodynamic forces - the forces which are on the blood when it enters, forces push out filtrate, maintain internal pressure of the blood supply, opposite oncotic force from all the stuff that stays in the blood attacks fluid back to it, vascular tone, struggles to cope with low blood volume

What are the differences between the two types of nephrons?

Cortical nephron makes up 88% of nephron mass and doesn’t go into the medulla, juxtamedullary nephron has a large loop of Henle that goes into the medulla, this is the one responsible for concentration urine, the core structures are the same

What is the juxtaglomerulra apparatus?

part of the distal tuble that contains macula densa cells it is a short, small, specialised part of the tuble, that is right next to the bowman’s capsule

What do macula densa cells do?

identify sodium and chloride ions in the blood, this turns on and off the RAS system, this helps with dehydration, if high sodium think have lots of water so turns RAS system off, activates RAS system through production of Renin

What history are you looking at with renal disease?

Fluid loss think about vomitting, diarrhoea, and sweating, illness, LUTS in men - lower urinary tract symptom normal due to enlarged prostate, previous UTI, PMH, family history

What examinations should you carry out around renal disease?

blood pressure, hypotention is a problem, look form pulmonary oedema or effusion, what is the volume status - is fluid in the wrong place

What are we looking for in a urine dip around renal disease?

bloods, proteins - small amount is normal - large amounts indicates segnificant damage to kidneys , nitratites and leukocytes - look for infection not >65,

What blood tests do you do around renal disease?

U and Es, FBC - anaemia?, low Ca2+?

What is GFR?

glomerulus filtration rate, the volume of filtrate produced by both kidneys each minute, the stuff downstream is just fine tuning so this is the bit that matters, inulin is infused into the patient for a day and regular urine and blood samples are taken to see where concentrations are

Why do we not normally use GFR?

laborious and expensive, only reserved for specific circumstances such as organ transplant and chemotherapy

What is albumin:creatinine ratio?

the amount of albumin in the urine compared to the amount of creatinine, used to diagnose kidney disease

When is creatinine produced? Why is this important?

produced when muscles broken down, amount is proportional to muscle mass, so only good when muscle mass is stable

Which equation is recommended to calculate function of kidneys (eGFR)? What are the varibles of the calaculation?

CKD epidemiology (EPI) equation, serum creatinine, age, race and sex

What are the units for eGFR?

ml/min/1.73m² - adjusted for body surface area

Can we use eGFR to diagnose kidney disease?

no, only use when someone has establised chronic kidney disease, look at trend to work out whether they are stabalising or declining

What are the common errors with eGFR?

likely to overestimate renal function in smaller patients, likely to underestimate renal function in larger patient, extreme body weights

What renal function equation do pharmacists use?

creatine clearance (CrCl) as takes into account someones weight and doesn’t use standardised body area, if someone has very little muscle mass we can use ideal body weight or if someone is very large, look in context of the trend as deit and muscle mass can effect it

Why do you need to think about CrCl and establised CKD?

creatine goes under renal reabsorbtion or tubular reabsorbtion, in the tubles creatine get secreated back into the body and back into the tuble, net value becomes squewed, this doesn’t happen in healthy kidneys as homoeostasis detects normal amount of creatine

What conditions/patient factors is CrCl used to esrtimate renal function in?

>75s, extremes of muscle mass >40 BMI use ideal weight, receiving treatment with narrow theraputic idex drugs

What is the CrCl equation?

(140-Age) x weight x constant/ serum creatine

What happens to serum creatine when an AKI occurs?

there is a delay before the serum creatine increases

What is chronic kidney disease?

reduction in kidney function or structural damage present for greater than 3 months, permanent and progressive disease, decreased GFR and albuminuria are independtly associated with higher risk of: all course mortality, cardiovascular mortality, progressive and AKI, more likely to die of CVD than need renal replacement therapy

What is the pathology of CKD?

Whatever causes the renal damage there will be a reduction in the flow of blood throught the nephrons, this results in fibrotic tissue forming, so reduction in nephron mass, the body diverts the rest of its blood to the functioning nephrons, glomerular hypertention in the functioning nephrons, this causes microtears and damage to the glomerus allowing large molecules through, proteinuria is detected by the body so reabsorbs different componants and cells in the proximal tubule, you get more cytokines, then more cell signalling, monocytic infiltration causes more fibrotic tissue to form, and the cycle repeats

What can fibrotic tissue do?

no functionality it just fills the gap