mock/ Flashcards
An example of normocytic anaemia is A. Iron deficiency B. Vitamin B12 deficiency C. Anaemia of chronic disease D. Haemolytic anaemia E. Folate deficiency
C. Anaemia of chronic disease
Choose the one incorrect statement
A. Supra renal glands are superior to kidneys
B. The liver is in direct contact with the right kidney
C. The duodenum is medial to the right kidney
D. The tail of the pancreas is anterior to the left kidney
E. The small intestine is medial to the left kidney
B. The liver is in direct contact with the right kidney
When referring to the cortico-medullary gradient what is the osmolarity of the medullary region of the kidneys A. 300 mosmol/L B. 900 mosmol/L C. 1400 mosmol/L D. 1200 mosmol/L E. 600 mosmol/L
D. 1200 mosmol/L
Which one of the following drugs should not be taken while breastfeeding? A. Warfarin B. Loratadine C. Tramadol D. Amoxicillin E. Enoxaparin
C. Tramadol
Which ONE of the following is not a possible cause of microcytic (iron deficiency) anaemia A. Poor iron intake from the diet B. Blood donation C. Taking NSAIDs D. Intrinsic factor receptor deficiency E. Gastro-intestinal disorders
D. Intrinsic factor receptor deficiency
Which One of the following is incorrect?
A. The normal bilirubin range is 3-21 micromol/L
B. Normal white blood cell count is 3-10x 109/L
C. The normal urea level is 2.5-6.5 mmol/L
D. The normal potassium level is 35-53mmol/L
E. Normal blood pressure range is 90/60 to 120/80 mmHg
D. The normal potassium level is 35-53mmol/L
should be 3.5-5.3
Which One of the following options represents the response of renal arterioles to a decrease in blood pressure to maintain GFR?
A. Afferent arterioles dilate, Efferent arterioles constrict
B. Afferent arterioles constrict, Efferent arterioles constrict
C. Afferent arterioles dilate, Efferent arterioles dilate
D. Afferent arterioles constrict, Efferent arterioles dilate
E. No response
A. Afferent arterioles dilate, Efferent arterioles constrict
What is the function of ADH in the kidney?
A. Increases water loss by inhibition of reabsorption via aquaporins
B. Increases loss of water in the filtrate
C. Acts as a pore so that water is reabsorbed into the blood
D. Signals for the placement of aquaporins in the apical and baso-lateral membranes allowing for movement of water from the blood to filtrate
E. Signals for the placement of aquaporins in the apical and baso-lateral membranes allowing for movement of water from the filtrate to blood
E. Signals for the placement of aquaporins in the apical and baso-lateral membranes allowing for movement of water from the filtrate to blood
Which is the main cell that is involved in destruction of beta cells in the pancreas in type 1 diabetes? A. T cells B. B cells C. Neutrophils D. Macrophages E. Eosinophils
A. T cells
What is meant by adverse drug reaction?
A. A noxious and unintended response to a drug that occurs at doses used for prophylaxis, diagnosis or therapy but response may not be due to that specific drug
B. An allergy to that specific drug
C. A noxious and unintended response to a drug that occurs at doses used for prophylaxis, diagnosis or therapy
D. Reactions are always dose related and predictable
C. A noxious and unintended response to a drug that occurs at doses used for prophylaxis, diagnosis or therapy
What is the most likely function of the proximal convoluted tubule?
A. Passive reabsorption of water only
B. Active transport of sodium
C. Active reabsorption of urea and hydrogen ions
D. Active transport of sodium and glucose
E. Regulate blood pressure, helping to release renin
D. Active transport of sodium and glucose
Which of the following has a rate of urinary excretion that is always much lower than its rate of glomerular filtration in a healthy adult? A. Urea B. Potassium C. Sodium D. Glucose E. Calcium
D. Glucose
Which one of the following is an accessory inspiratory muscle? A. Internal intercostal B. External intercostal C. Internal oblique D. Rectus abdominus E. Diaphragm
B. External intercostal
Which of the following options is characteristically involved in the initial response in acute inflammation?
A. Constriction of arterioles
B. Capillary endothelial cell enlargement
C. Influx of macrophages
D. Influx of mast cells
E. Influx of neutrophils
E. Influx of neutrophils
How does activated Vitamin D directly maintain normal serum calcium
A. Decreases calcium absorption from the intestinal lumen
B. Increases calcium release from bone
C. Increases calcium reabsorption from the kidney tubule
D. Decreases calcium reabsorption from the kidney tubule
E. Increases calcium release from the stomach
C. Increases calcium reabsorption from the kidney tubule
What renal compensation takes place for respiratory alkalosis?
A. Less renal excretion of bicarbonate ions and less renal absorption of hydrogen ions
B. More renal excretion of bicarbonate ions and more renal absorption of hydrogen ions
C. More renal excretion of hydrogen ions and more renal absorption of bicarbonate ions
D. More renal excretion of carbon dioxide
E. Less excretion of carbon dioxide
B. More renal excretion of bicarbonate ions and more renal absorption of hydrogen ions
Which one these statements correctly explains the hygiene hypothesis?
A. Decrease in allergic disease is due to reduced exposure to pathogen
B. Increase in allergic disease is due to reduced exposure to pathogen causing a decreased default Th2 differentiation
C. A decreased default Th1 differentiation
D. An increase in allergic disease is due to reduced exposure to pathogen causing a increased default Th2 differentiation
D. An increase in allergic disease is due to reduced exposure to pathogen causing a increased default Th2 differentiation
Tetracycline in children is contraindicated as it can lead to A. Grey skin colour B. Reyes syndrome C. Discoloured teeth D. Rash, vomiting and fever E. Liver damage
C. Discoloured teeth
Which of the following statements about erythropoietin is false?
A. Recombinant EPO is licensed for anaemia in chronic renal failure
B. Receptors are homodimeric and situated on red blood cell precursors
C. Receptors on cardiac tissue indicate cardioprotective properties
D. At normal oxygen levels HIF 1 alpha is not hydroxylated so EPO transcription does not occur
E. Inability to produce EPO is linked with reduced exercise capacity
D. At normal oxygen levels HIF 1 alpha is not hydroxylated so EPO transcription does not occur
What effect does TNF alpha not have in rheumatoid arthritis
A. Cause bone erosion via osteoclasts
B. Causes cartilage destruction
C. Has a positive feedback effect of inflammatory cytokines
D. Increases the chance of activating latent TB
E. Causes loss of muscle mass (sarcopenia)
D. Increases the chance of activating latent TB
Which of the following is not an effect of fluid overload from chronic kidney disease A. Hyponatraemia B. Hypernatraemia C. Pulmonary oedema D. Pitting oedema E. Hypertension
B. Hypernatraemia
Which one of the following describes oral allergy syndrome?
A. High sensitisation to storage proteins within peanuts; high risk of anaphylaxis
B. Cross-reactivity with lipid transfer proteins in peanuts; moderate risk of systemic reactions
C. Cross-reactivity with ubiquitious and unstable plant proteins; tingling and itchiness only
(Normally confined to the lips mouth and throat)
C. Cross-reactivity with ubiquitious and unstable plant proteins; tingling and itchiness only
What is the function of Th2 cytokines in type 1 hypersensitivity?
a) To help bind IgM to bind to neutrophils
b) Class switch to IgE
c) To allow B cells to produce histamine
d) To send signals for mast cells to degranulate
b) Class switch to IgE
Which drug treats autoimmune disease by blocking pathways involved in nucleotide synthesis? A. Azathioprine B. Prednisone C. Colchicine D. Dapsone E. Aspirin TPMPT activity
A. Azathioprine
What diuretics can cause gout? A. Carbonic anhydrase inhibitor B. Aldosterone antagonist C. Thiazide and related diuretics D. Sodium channel blocker E. Loop diuretics
C. Thiazide and related diuretics
which is least likely to cause AKI? A. Hypervolaemia B. Hypokalaemia C. Sepsis/infections D. Drugs E. BMI
A. hypervolaemia (fluid overload)
B. Hypokalaemia (volume depletion = aki)
C. Sepsis/infections (sepsis associated acute kidney injury)
D. Drugs (diuretics and many more – aki)
E. BMI (risk factor?)
Which structures are present in the medullary region of the kidney? A) Loop of Henle and collecting ducts B) Loop of Henle and PCT C) PCT and glomeruli D) Glomeruli and DCT E) DCT, PCT, glomeruli and Loop of Henle
A but: Collecting ducts, loops of henle, vasa recta and the interstitium
Regarding teratogenicity, which of the following statements is incorrect?
a) The embryonic period, during which organogenesis takes place (1st trimester) is when a foetus is most at risk of teratogenic effects
b) Hydralazine, Labetalol, and Nifedipine are the recommended first-line treatments for severe hypertension in pregnancy (pre-eclampsia)
c) Ramipril and Lisinopril are the recommended first-line treatments for hypertension in pregnancy (methyldopa is used 1st line)
d) Teratogenic drugs can affect growth and functional development or have toxic effects on tissues (fetotoxicity) in the 2nd and 3rd trimester
e) Sodium Valproate is contraindicated in pregnancy as it causes birth defects such as spina bifida
c, methyldopa = 1st line
What are the characteristics of metabolic acidosis?
A) a high pH, high HCO3- and the loss of H+ ions and addition of HCO3- ions
B) a high pH, low PaCO2 and the reduction of H+ ions
C) a low pH, high HCO3- and the loss of H+ ions and reduction HCO3- ions
D) a low pH, high PaCO2 and the addition of H+ ions (resp)
E) a low pH, low HCO3- and the addition of H+ ions and reduction HCO3- ions
E) a low pH, low HCO3- and the addition of H+ ions and reduction HCO3- ions
Which ONE of the following statements about anaemia is INCORRECT?
A. Anaemia of chronic kidney disease can be mild microcytic anaemia
B. Vitamin B12 deficiency can increase MCV
C. Haemolytic anaemia can increase MCV
D. Iron deficiency anaemia show increased MCV
E. Coombs positive patient show fragmented red blood cells on blood film
D. Iron deficiency anaemia show increased MCV
(microcytic)
(coombs = you have antibodies that act against your red blood cells)
(macrocytic anemia can be due to b12 or folate deficiency)
Haemolytic – rbc destroyed faster than made
Macrocytic anemia - body has large rbc and not enough rbc
Microcytic – small, red blood cells characterized by low mcv (ida – most common cause)
What the does the presence of IgM indicate:
• Activation of b cells
• A recent exposure has taken
• An allergic rection is present
• A reaction between mother and fetus across the placenta
• Activation of memory cells
• A recent exposure has taken
IgM antibodies = detection technique for diseases
How does renal failure cause oedema?
Renal odema is associated with renal sodium retention.
CKD impairs excretory renal function. What occurs if excretory function of kidney fails.
A- Decrease in nitrogenous waste
B- Increase in absorption of urate (increased retention serum uric acid that occurs as gfr decreases, slow down in the removal of uric acid from the body)
C-Retention of phosphate
D- Increase in creatinine release through urine
C-Retention of phosphate - Normal working kidneys can remove extra phosphorus in your blood, in CKD this cannot occur. Extra phosphorus puls calcium into bones
What is desmopressin and whats its role?
Analogue of vasopressin (ADH) released from the anterior pituitary
Limits hm water eliminated at the kidney (an antidiuretic!)
When bound to V2 receptors in the kidney it: Increased tubular water permeability Enhances water reabsorption Extracellular fluid = more dilute Urine = more concentrated
desmopressin is a selective V2 receptor agonist… but it doesnt cause unwanted vasoconstriction- why?
Selective V2 receptor agonist – retains the antidiuretic activity of vasopressin but lacks the pressor activity so doesn’t cause the unwanted vasoconstriction
what does desmopressin do when bound to V2 (ADH) receptors in the kidney? affect?
Increased tubular water permeability
Enhances water reabsorption
Extracellular fluid = more dilute
Urine = more concentrated
Does ADH promote dehydration?
when DEHYDRATED…
ADH reduces water loss via lowered urine volume. Extracellular dehydration (hypovolaemia) stimulates specific vascular receptors that signal brain centres to initiate drinking and ADH release.
what stimulates specific vascular receptors that signal brain centres to initiate drinking and ADH release?
hypovolaemia (extracellular dehydration)
licensed indications of vasopressin? (BNF uses)
Diabetes insipidus (treatment or diagnosis)
Primary nocturnal enuresis
Post-op polyuria or polydipsia
Polyuria or polydipsia after hypophysectomy
Idiopathic nocturnal polyuria
Nocturia associated with MS
Renal function testing
Mild to moderate haemophilia and von Willebrand’s disease
Fibrinolytic response testing
Lumbar puncture associated headache
how can head injury cause Diabetes insipidus?
problems with ADH/ vasopressin (AVP)
AVP is produced by the hypothalamus and stored in the pituitary gland until needed
thus cause = PITUITARY TUMOUR form head injury or surgery damage
what can affect V2 (vasopressin/ ADH) receptor function?
gene mutation
what does desmopressin act on to increase expressino of what?
Acts on V2 receptors
Increases expression of aquaporins
More water reasoned into interstitium of kidneys
what happens if lack of vasopressin/ ADH
ADH released when dehydrates, says ‘bring back water!’- reabsorb
cannot signal kidneys so its all flushed out in urine
Desmopressin conserves some water so its not all flushed out. Only to small amount, large amount would lead to water intoxication.
= =kidneys may excrete too much water. This causes frequent urination and can lead to dehydration, as well as low BP
diabetes insipidus!!
what do vasopressin and analogues promote?
and whats their affect
: Regularly release ADH: promote insertion of water channel proteins (AQP2) into apical membranes of cells in renal collecting ducts. Cells now have increased permeability to water, more water reabsorbed. Less water lost in urine.
Differentiation between DI and nephrogenic diabetes insipidus?
DI: body doesn’t produce Vasopressin
Nephrogenic diabetes insipidus: body produces Vasopressin but kidneys aren’t responding to it.
(like T1/2DM)
what is the difference between the two molecules and how does this affect their pharmacology
desmopressin + vasopressin
VP:
- (Only available as solution for injection)
- More selective for V2 receptors on collecting duct = more potent. Therefore less vasoconstrictive effect
- Short half life- administered every 4 hours.
- Rapid elimination
- Can’t use IV not licensed for use in DI patients anyway.
- 3 vasopressin receptors: v1,V2,V2. All have diff functions.
what the desmopressin is for, how it works and why he needs to use it for DI?
DI = polydipsia and polyuria (extreme thirst and frequent urination).
- Not enough ADH in body (role of dec urine production) so must be given as medication.
- Desmopressin: more powerful than endogenous ADH, stop kidneys producing urine.
- Regulates water in body and alters hm brought back from kidney
what would happen if patient stops takinig desmopressin for DI.
(hint- serum and urine osmolality changes)?
Apical memb. ADH ↑ aquaporins on memb so ↑ water can get through and be absorbed
Basolateral: always has aquaporins
V1: smooth muscle contraction in cardiovascular system
V3: promote ACh release via this receptor
Calculated osmolality = 2 x serum sodium + serum glucose + serum urea (all in mmol/L).
Uosm = 1.25 × urea (mmol/l)
Dilute, pale urine
Become more thirsty
Serum osmolality: ↑ as serum Na ↑ More mols in blood = ↑ serum osmolliy. ↑ water in blood = lower serum osmolality
Urine osmolality ↑
Other symptoms: Fatigue, anorexia, weight loss
ADH effects and drugs: NSAIDs, Li, ethanol?
NSAIDs: Naproxen, carbamazepine: used for seizures.
Increase action of ADH- urine more concentrated
Li: for bipolar disorder. Inhibits ADH. More dilute urine produced
Ethanol inhibits secretion of ADH
osmolality and osmolarity units?
Osmolarity: mmol/L easier to measure. As sample given in ml and L
Osmolality: mmol/kg more accurate
why should patient with DI not drink excessively/ drink lots of mineral energy drinks?
Should be guided by thirst else: hyponatraemia - reduction in conc of Na in blood. More water retention
Homeostasis is achieved through the process of what?
glomerular filtration of
plasma to produce an ultrafiltrate. The tubules then process this
ultrafiltrate so that the final urine flow rate and solute excretion meet
the homeostatic needs of the body.
In the steady state, our total body water content and salt content
remain constant. An increase or decrease in water and salt intake is
paralleled by an equivalent change in renal water and salt excretion.
Osmolality and osmolarity are measurements of ?
solute concentration of a solution. In practice, there is negligible difference between the absolute values of the different measurements.
Calculated osmolarity equation
= 2 (Na+) + 2 (K+) + Glucose + Urea
(all in mmol/L);
Mrs Brown’s calculated osmolality
= (2 x 118) + (4.9 x 2) + 4.6 + 4.8
= 255mOsm/l
comment on the value
Normal is around 285 !
Or serum Na x 2 + serum potassium x 2 + urea + glucose
All in mmol/L
plasma osmolality is a guide to
intracellular osmolality. why?
cell membranes in general are freely permeable to water, the
osmolality of the extracellular fluid (ECF) is approximately equal to that of the intracellular fluid (ICF).
In normal people, increased osmolality in the blood will stimulate secretion of what?
ADH -> inc water reabsorption, more conc urine, less conc blood plasma
elevation of ADH may be associated with what?
stroke mortality
– associated w DI
possible causes of:
normal/high serum osmolality
high urine osmolality (conc)
- Dehydration
- Renal disease and uraemia
- Congestive heart failure
- Addison’s disease
- Hypercalcaemia
- Diabetes mellitus/hyperglycaemia
- Hypernatraemia
- Alcohol ingestion
- Mannitol therapy
possible causes of:
normal/high serum osmolality
low urine osmolality (dilute)
DI !
possible causes of:
LOW serum osmolality
HIGH urine osmolality (conc)
Syndrome of inappropriate ADH secretion
SIADH
possible causes of:
LOW serum osmolality
LOW urine osmolality - w no inc in fluid intake
(dilute)
-Overhydration
•Hyponatraemia
•Adrenocortical insufficiency
•Sodium loss (diuretic or a low-salt diet)
whats urine osmolality in dehydration?
very high as very conc!
800-1400mOsm/kg
whats SIADH?
syndrome of inapp ADH secrtn
Inappropriately concentrated urine in the setting of a low plasma
osmolality – inappropriate ADH production and release (TOO MUCH!)
SIADH causes
Brain and spinal cord conditions, such as a direct injury, infection,
or fluid buildup
Cancer
Lung conditions, such as COPD, pneumonia, or tuberculosis
Drugs: usually those used to treat diabetes, cancer, or depression
Family history of SIADH
Too much physical pain or stress on your body
1How would investigating the urine help confirm if SIADH happening?
Urine would be in little volumes and more concentrated as ADH inhibits urine production.
Check for urinary sodium excretion >30mmol/L
SIADH Symptoms
Tiredness and weakness
Muscle pain, cramps, or headaches
Dark urine or changes in how much urine is produced
Decreased appetite for food, or increased thirst
Diarrhea or constipation
Nausea or vomiting
Seizures
Trouble thinking clearly, or hallucinations
What to do. about SIADH?
- Investigate the cause (more bloods, chest x-ray, CT scan,
check drug history) - Can be corrected with an AHD V2 receptor ANTAGONIST
“vaptans” = Tolvaptan
common feauture of SIADH?
very low urine osmolality! e.g. 180
should be 500-850
What medical conditions and medications can lead to overproduction ADH hormone?
(SIADH)
T2DM drugs,
antidepressants,
brain injury, brain infection, brain abscesses, subarachnoid hemorrhage
Epilepsy head trauma infections autoimmune…
Cancers
Lung disease
whichi drugs best to treat SIADH:
increase excretion of free water whilst minimising excretion of sodium into urine= correct serum sodium concentration and serum osmolality. ?
Diuretics
help rid your body of salt (sodium) and water. Most of these medicines help your kidneys release more sodium into your urine. The sodium helps remove water from your blood, decreasing the amount of fluid flowing through your veins and arteries.
Fluid restriction recommended
V2 receptor antagonist !! VAPTAN selective for V2 receptors
monitoring with VAPTAN for SIADH?
Serum sodium: measure every 6 hours after starting treatment for first 2 days.
Renal function test
check again
acid base and angiotensin system SGT
What standards should you meet if you are offering to check peoples blood pressure?
Relaxed setting adequate training and reviews equipment regularly calibrated and maintained cuffs should be appropriate tablets ask for consent
what BP checks to do on elderly?
sitting and standing BP to check for postural hy[ptension: risk of falls
What should you check on patients before taking their bp and why?
Pulse to check for irregularities in heartbeat/ flutter due to AF
What stage of hypertension is a reading of 162/101?
stage 2
What may be offered to confirm a diagnosis of hypertension without risk of white coat syndrome?
ABPM
what to offer t patietn diagnosed with stage 2 hypertension?
antihypertensives (diuretics spec thiazide d - bendroflumethiazide etc) lifestyle advice: - dietary salt - alcohol consumption - physical activity - mental health
Patients with suspected hypertension must also be investigated for target organ damage. What might an ECG be used to see the development of?
AF
additional tests for stagge 2 hypertension?
target organ damage
hypertensive retinopathy
LV hypertrophy on ECG
blood tests: serum elec, creat, eGFR, fasting gluc and lipids, Na, K in urea
urinalysis for proteins. may cause kidney damage
blood gluc leveks: HbA1c
What tool may be used to assessed CVS risk?
QRISK3
What non-pharmacological and dietary advice to stage 2 hypertensive patieht
Control + improve diet -reduce risk of heart problems:
• e.g. use wholegrain bread, and brown rice.
• min 5 portions fruit + veg a day.
• low-fat foods - avoid lot of fat and sugar.
• Reduce excessive caffeine consumption, low dietary sodium intake (reduce or substitute any sodium salt).
• Cut alcohol intake.
• Avoid some exercises: sprinting/ weightlifting as they raise your blood pressure rapidly and put strain on heart and blood vessels
Decreasing salt intake decreases BP
• Less Na, K, Cl ions in ascending LoH
• No reabsorption into medullary interstitium
• Prevent cortico-medullary gradient forming
• More urine produced, decreased Na reabsorption so more excreted,
• Blood volume and pressure decreased.
Caffeine: stimulant increases HR and maybe anxiety. Check how much he drinks
Signpost local support networks
whats BP regulated by?
BP regulated by macula densa of DCT and afferent arteriole = juxtaglomerular apparatus.
Why might a Hb1ac test be carried out in patients with hypertension?
Average blood glucose of last 2-3 months, check if patient is diabetic, shows how much sugar has glycosylated in this peroid
How would you physiologically explain the rationale behind the dietry advice regarding dec salt intake?
increased salt means body retains water
increases plasma volume
puts pressure on blood vessels
can worsen bp
What drug and class would be recommended to a white man under the age of 55 diagnosed with hypertension? 1st line
what if this is not well tolerated?
ACEi such as ramipril
look at most cost effective one and ones with best patient compliance (OD)
or ARB if ACE not tolerated. DO NOT COMBINE
why ACEi first line in hypertension (most of the time)
Reduce blood pressure by relaxing blood vessels. Usually first line and inhibit RAAS.
….
Potent stimulation of Na reabsorption from PCT so blood volume hence BP increased. Opposite true for the drugs. Renin release inhibited so less ACE enzyme levels in body, decreased BP.
What side effects would you warn patients starting Acei about?
- common: dry cough, if excessive refer back to GP, swap to ARB
- angioedema so look for swelling of lip and throat
take first dose at night to reduce first dose hypotension until bp stabilised and then go to morning dose - hyperkalaemia (excess K levels in blood arrythmias) monitor after 2 weeks- blood test for kidney function and can see K levels, fatigue, dizziness as lower BP (hypotension), headaches, loss taste.
Diarrhoea- nausea and vomiting- become dehydrated
Reduce arteriolar- vasoconstriction
Don’t stand up very quickly etc as may feel dizzy and have falls.
Get up out of bed- sit on bed for a bit
Why may a dry cough develop in patients who are on Acei?
ACE breaks down bradykinins in lungs
If inhibited these accumulate
hence cough develops
Outline how Acei such as captopril work?
Inhibit the ACE enzyme
Ang I cannot be converted to ang II
Blocks release of aldosterone causing vasodilation and relax of blood vessels and water loss
therefore reduces blood vol and blood pressure
better blood flow through kidneys
Acei retain potassium which can lead to the risk of developing?
hyperkalaemia
What monitoring is required with Acei?
Renal function and electrolytes (Na/Cl) before and 2 weeks after starting
every 3-6 months thereafter
as May cause frop in renal perfusion pressure thus drop in (GFR), renal failure possible. Also increase creatinine levels
Why is monitoring needed for Acei and what could be the consequences if this isnt done?
Lowering BP affects renal perfusion
potential to cause renal impairment and failure
Acei can worsen hyperkalaemia and renal failure hence want to monitor
mild consequneces can be nausea
severe can lead to arrythmia and cardiac arrest
Diarrhoea and vomiting in patients taking Acei may mean dehydration and worsening of renal impairment. What would you recommend the patient to do?
Stop taking the acei for a few days
Which other classes of drug inhibit activity of the renin-angiotensin system other than ACEi?
ARBs (Ang II rec blockers)
renin inhibitors
aldosterone rec antagonists
How do ARBS inhibit the RAS system?
Angiotensin receptor blockers prevent the binding of ang II at the site
Why do patients on Acei no longer get a dry cough when switched to ARBS?
bradykinins continue to be broken down therefore are not accumulating
What do renin inhibitors do?
Prevent the conversion of angiotensinogen to angiotensin I
Why are some populations not recommended acei as first line?
Afro carribean populations recommedend CCBs instead as they dont respond well to ACEi and are at a higher risk of angioedema
What metabolic abnormality is demonstrated by these results:
pH - 7.09
PaCO2 - 3.6 kpa
PaO2 - 15 kpa
HCO3 - 8mmol/L
metabolic acidosis
pH - 7.09 low
PaCO2 - 3.6 kpa too low
PaO2 - 15 kpa acceptable
HCO3 - 8mmol/L too low
What is the normal range for bicarbonate in the blood?
22-26 mmol/l
clinical consequences is metabolic acidosis left untreated?
Death and organ failure. esp of have impaired kidney function anyway
Why might patients experincing metabolic acidosis also experience breathlessness?
trying to blow out in an attempt to raise pH to normal
OR
Breathlessness may be due to heart attack- blood can’t travel to tissues quick. Low CO2 in response to that
What are clinical consequences if metabolic acidosis is left uncorrected?
Causes insulin resistance leading to diabetes
decreased cardiac output leading to hypotension
Altered oxygen delivery
decreased atp production
denaturing of enzymes leading to organ failure
When sodium bicarbonate is given to restore the serum bicarbonate levels, why is the increase in small increments?
to prevent levels going to high
Sodium bicarbonate replacement q
If the volume of distribution of HCO3- is approximately 0.5 mmol/kg body weight and Mrs Begum weighs 70kg how much sodium bicarbonate does the team need to give Mrs Begum to restore the serum bicarbonate to 24 mmol/L? (currently: 8mmol/L)
Bicarbonate deficit
= Vd x weight (kg) x (bicarb range you want – actual)
= 0.5 x 70kg x (24-8)
= 560mmol NB: Is an approximation!
BNF Products:
1) 1.26% Sodium bicarb 500ml
2) 8.4% Sodium bicarb 200ml
1.26g in 100ml (11.9/1 x 1.26 = 15mmol in 100ml)
12.6g in 1000ml = 150mmol in 1L
600mmol in 4L
Nearly 4l required of 1.26%, high risk in patient with MI
as a lot of Na and big volume
Less volume with 8.4% but very hyperosmolar!!!!
know the dangers and precautions if infusing 8.4% bicarbonate and as with all treatment, the monitoring parameters and consequences of over correction.
8.4% only need 500mL roughly.
But very potent. Into small veins. Alkaline, necrotic, inflammation
Should be put into central vein not peripheral.
monitor (ongoing)
- ABG analysis: minimise possibility of overdose and alkalosis
- Serum electrolytes: replacement of Ca, Cl, L important if alkalosis occurs. Too rapid correction of Na = severe neurological effects.
- Fluid balance: excess Na retained, extracellular fluid excess may be retained, peripheral oedema
- Acid base balance: bicarbonate induced metabolic alkalosis can occur. Na is associated with chloride and bicarbonate in the regulation of acid–base balance.
Na Ca K pH
difference between HCO3 in
- resp alkalosis
- metab alkalosis?
- LOW
- HIGH
SGT: Reduced Renal Clearance
whats morphine and how does it work?
: strong painkiller, works by blocking signals from travelling along nerves to the brain. Common side effects: constipation, feeling sick and sleepiness. Can become addicted to morphine if treatment not properly reviewed.
What are the usual adverse effects of morphine?
Morphine is an opioid, effects are related to agonist activity at mu receptors: expect drowsiness, dizziness, spiritual depression, dry mouth, nausea, vomiting, confusion, flushing, constipation. For all opioids, adrenocortical insufficiency possible: reduce dose.
Expect constipation: occurs via stimulation of mu-opioid receptors on myenteric plexus, inhibits gastric emptying and reduces peristalsis. Should prescribe stimulant laxative with this.
Reduced GI motility = com=nstipation
Other side effects include:
Serious allergic reaction which causes difficulty in breathing or dizziness; swelling of the eyelids, face or lips; rash or itching (especially affecting your whole body). If you are affected by these important side effects contact a doctor immediately.
Respiratory depression
CNS suppression
Very common: may affect more than 1 in 10 people
• feeling sick (nausea)
• vomiting
• shallow breathing
• constipation
• sleepiness
• not knowing where you are (disorientation)
• sweating
• a perception of seeing or hearing things (hallucinations)
• uncomfortable mood
• feeling of very intensive happiness and wellbeing (euphoria)
• tolerance and dependence (with long-term treatment)
What are the usual adverse effects of morphine?
opioid, effects related to agonist activity at mu receptors:
drowsiness, dizziness, spiritual depression, dry mouth, nausea, vomiting, confusion, flushing, constipation.
For all opioids, adrenocortical insufficiency possible: reduce dose.
Other side effects include:
Serious allergic reaction which causes difficulty in breathing or dizziness; swelling of the eyelids, face or lips; rash or itching (especially affecting your whole body). If you are affected by these important side effects contact a doctor immediately.
Respiratory depression
CNS suppression
Very common: may affect more than 1 in 10 people
• feeling sick (nausea)
• vomiting
• shallow breathing
• constipation
• sleepiness
• not knowing where you are (disorientation)
• sweating
• a perception of seeing or hearing things (hallucinations)
• uncomfortable mood
• feeling of very intensive happiness and wellbeing (euphoria)
• tolerance and dependence (with long-term treatment)
common side effecr of morphine and what may be prescribed alongside?
constipation: occurs via stimulation of mu-opioid receptors on myenteric plexus, inhibits gastric emptying and reduces peristalsis. Should prescribe stimulant laxative with this.
Reduced GI motility = constipation
morphine metabolism and clearance from body?
Excreted renally (10%) Metabolised to codeine and glucose indies (3 and 6) in liver
Also metab to Normorphine
Metabolite: M6G contributes most to analgesic effect
M3G and M6G cleared by kidneys
Poor oral bioavailability 15-64% very variable
If half-life of morphine is unchanged in renal failure why is patient exhibiting severe signs of opiate toxicity?
( clearance of the different morphine metabolites and pharmacological properties)
• Dose too high? Calculate using dose adjustment table
• Extreme caution with all opiates in patients with impaired renal function
• Potential accumulation of M6G (active metabolite, more potent than morphine) and M3G.
• Half life of M6G increased from 3-5 hours in normal renal function to about 50 hours in ERF (established renal failure)
Caused by respiratory depression: ..
Due to accumulation of metabolites
M6G: high affinity for opioid receptors
High Half life = accumulate and toxicity
drug for OD of morphine in reduced renal clearance?
Naloxone (opioid receptor antagonist, for acute opioid overdose–high-dose regimen [when rapid titration with naloxone is necessary to reverse potentially life-threatening effects]) readily available: initially 100mcg-200mcg then 100mcg up to 2 doses at 1 minute intervals.
Rapidly reverses opioid overdose. Attaches to opioid receptors and reverses and blocks effects of other opioids. Will cause an increase in mean aortic pressure, cardiac output.
rapidly absorbed after oral administration, but this route may not be ideal due to high metabolism (pre-systemic).
Given IV/ IM
Start at 400mcg, can go up to 2mg
M6G 10-15 hours half life
Naloxone: 1-1.5 hours half life (SPC!!)
Therefore have to administer naloxone multiple times to prevent effect wearing off and opioid toxicity coming back.
how is morphine excreted?
renally: thus has those side effects
consider patient eGFR and titrate
Safest opioids in patients with renal failure
Fentanyl,
- not renally excreted
- transdermal patch
- BUT time takes to titrate dose etc… not best option
hydrocodone,
- renal exc
- half life prolonged in renal failure
Tramadol:
Excreted renally, not strong enough (not pure opioid analgesic) wont have best effects
Methadone:
Used to help treat addictions
Fewer SEs and active forms than morphine
Must be admin by specialist for pain due to pharmacokinetics
consequences of inapp dose of aciclovir in immunocomp patient?
Acute kidney injury
Or increased risk of adverse effects
Has to maintain adequate hydration: to reduce renal complications. Aciclovir excreted in urine unchanged = crystals in urine, want to avoid
SGT: Calcium and Phosphate
normal phosphate levels in dialysis?
- 8 – 1.5 mmol/L normal
1. 1 - 1.7mmol/L dialysis: higher as less effective than kidneys, difficult to correct to normal artificially.
whats phosphate needed for? (4)
Phosphate is a charged ion containing the mineral phosphorous. This mineral is needed by the body to build and repair bones and teeth, help nerves function, and make muscles contract.
Needed for:
• Muscle function
• Heart (cardiac) function
• Bone metabolism
• Cellular functions: energy metabolism and cell signalling
why is parathyroid gland likely to be overactive if phosphate is high?
Kidneys not excreting phosphate, so goes up, PTH increases too
PTH want to get rid of more but can’t as kidneys not working properly.
PTH trying to mobilise Ca and phosphate too as a result.
PTH increases osteoclast activity to increase serum Ca
role of Ca phosphate binders? commonly sevelamer and lanthanum
suppress parathyroid hormone concentrations
PTH regulates levels of calcium and phosphate in blood, work by homeostasis and both are regulated by pathways involving vitamin D. Calcium given to increase calcium levels, therefore decrease phosphate levels back to normal.
non-pharmacological measures to reduce serum phosphate concentration
Renal dietician:…
Milk, red meat, dairy, grains, legumes, chocolate, beer
Difficult to avoid
difference in vitamin D in multivitamin and the alfacalcidol
vitamin revision in general
Alfacalcidol: given in active form (kidney cant currently convert so multivitamin)
Vit D, K, A(too much is toxic) fat soluble
Water soluble vitamins (C) just get excreted, not stored
Vit K needed for clotting factors
Need afacalcidolin hydroxylated form to be active.
Supplement with water soluble vitamins not fat soluble
possible adverse effects of taking both calcium acetate and alfacalcidol
what to monitor?
Hypercalcaemia!! monitor plasma calcium concentration, check weekly/fortnightly intervals.
Constipation, anorexia, levels increase, more nausea vomiting… delirium, coma
2.6: levels getting high
Higher than 3: needs immediate treatment
At risk: renal patients
Malignant matasticies (bone)
Also monitor phosphate!
hypercalcaemia causes
result of overactive parathyroid glands.
cancer, certain other medical disorders, some medications, and taking too much of calcium and vitamin D supplements.
What is cinacalcet and how does it reduce overactivity of parathyro?
Bone resorption inhibitor drug- lowers PTH, -> decrease in serum Ca concs, improve hyperparathyroidism problem
Increase sensitivity of Ca receptors. Reduce PTH released. Secondary Hyperpara (as caused by renal)
What are the potential serious side effects of taking cinacalcet
Hypocalcaemia: paresthesia, muscle spasms, cramps, tetany, circumoral numbness, and seizures.
Can also prolong QT interval, more risk of ventricular arrhythmias (so do some drugs- methadone)
