Week 4 Flashcards

1
Q

How does the nephrotic syndrome cause oedema?

A

Disorder in glomerular filtration results in protein (mainly albumin) appearing in urine, causing proteinuria

Loss of protein = decreased oncotic pressure = increased formation of interstitial fluid which causes oedema

Increased fluid in the interstitium also = less blood volume and cardiac output = activation of RAAS = retention of Na+ and H2O = oedema

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2
Q

How does congestive heart failure cause oedema?

A

Reduced cardiac output = renal hypoperfusion = activation of RAAS

RAAS activation results in expansion of blood volume = increased pressure in vessels, plus reduced osmotic pressure = pulmonary and peripheral oedema

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3
Q

How does hepatic cirrhosis with ascites cause oedema?

A

Increased pressure in the hepatic portal vein + decreased production of albumin = loss of fluid into peritoneal cavity and ascites

RAAS activated in response to decreased circulating volume

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4
Q

What is secreted and reabsorped at the proximal convoluted tubule?

How permeable is this segment of the nephron to water?

A

Secreted

  • glucose
  • ions
  • H2O
  • amino acids

Reabsorbed

  • urea

Highly permeable to water

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5
Q

What is secreted at the descending limb of the Loop of Henle?

How does this affect osmolarity inside the nephron?

How permeable is this segment of the nephron to water?

A

Water is secreted but NaCl is retained

This causes the osmolarity inside the tubule to rise

This segment is highly permeable to water

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6
Q

What is secreted at the ascending limb of the Loop of Henle?

How does this affect the osmolarity within the tubule?

How permeable is this segment of the nephron to water?

A

NaCl is secreted, but water is retained

This causes the osmolarity within the tubule to fall

This segment is completely impermeable to water

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7
Q

What is reabsorbed at the distal convoluted tubule?

How permeable is this segment of the nephron to water?

A

H2O

Ca2+

Na+

Cl-

This segment is variably permeable to water

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8
Q

What is secreted at the collecting duct?

How permeable is this segment of the nephron to water?

A

H2O

Ca2+

Na+

Cl-

This segment is variably permeable to water

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9
Q

What diuretics target the proximal convoluted tubule?

What specifically do they target here?

A

Carbonic anhydrase inhibitors e.g. acetazolamide

Target the Na+/H+ exchanger

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10
Q

What diuretics target the Loop of Henle?

What specifically do they target here?

A

Loop diuretics e.g. furosemide and bumetanide

Target the Na+/K+/Cl- triple co-transporter

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11
Q

What diuretics target the distal convoluted tubule?

What specifically do they target here?

A

Carbonic anhydrase inhibitors e.g. acetazolamide

Also Thiazide diuretics e.g. chlorothiazide, indapamide

Carbonic anhydrase inhibitors target Na+/H+ exchange

Thiazides target the Na+/Cl- co-transporter

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12
Q

What diuretics target the collecting tubule?

What specifically do they target here?

What is the benefit of this particular group of diuretics?

A

Potassium-sparing diuretics target the collecting tubule e.g. spironolactone, eplerenone, amiloride and triamterene

Potassium-sparing diuretics target Na+/K+ exchange. By blocking Na+ reabsorption here, these drugs inadvertantly block K+ secretion, thus avoiding hypokalaemia

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13
Q

Why does even a small inhibition of reuptake of NaCl in the kidneys have a significant increase in Na+ excretion?

A

Because the vast majority of NaCl and H2O that passes into the filtrate via the glomerulus is reabsorbed

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14
Q

The site of action of many diuretic drugs is the apical/basolateral membrane of the tubule

A

Apical membrane

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15
Q

What transport system is used in to move acidic drugs into the renal tubule?

Give some examples of diuretics that operate via this system

A

Organic Anion Transporters (OATS)

Diuretics using these tranporters include thiazides and loop diuretics

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16
Q

What transport system is used in to move basic drugs into the renal tubule?

Give some examples of diuretics that operate via this system

A

Organic Cation Transporters (OCTs)

Diuretics using these tranporters include triamterene and amiloride (both potassium-sparing diuretics)

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17
Q

Name some Loop Diuretics

What do they target?

This type of diuretic acts rapidly/slowly

A

Furosemide, Bumetanide

Target the Na+/K+/Cl- triple co-transporter by binding to the Cl- site

Rapid onset following IV administration

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18
Q

What other benefit do loop diuretics confer when used to treat pulmonary oedema caused by heart failure?

A

Have an additional indirect venodilator action

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19
Q

What are some of the clinical indications for using loop diuretics?

A

To reduce salt and water overload in…

  • Acute pulmonary oedema
  • CKD
  • Hepatic cirrhosis with ascites
  • Chronic heart failure
  • Nephrotic syndrome

To increase urine volume in acute kidney failure

To treat hypertension

To treat acute hypercalcaemia

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20
Q

What are some of the potential side effects of loop diuretics?

A

Hypokalaemia

Metabolic acidosis

Hypovolaemia and hypertension (especially in the elderly)

Depletion of Ca2+ and Mg2+

Hyperuricaemia = gout

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21
Q

What do thiazide diuretics target?

Give some examples of this class of drug

A

They target the Na+/Cl- co-transporter on the apical membrane in the distal convoluted tubule

Bendroflumethiazide

Indapamide

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22
Q

What is the main adverse effect associated with thiazide diuretics?

A

Hypokalaemia

They do this by inhibiting the Na+/Cl- carrier via binding to the Cl- site, which results in an increased Na+ load being delivered to the distal tubule, and which in turn causes a loss of K+

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23
Q

What addititonal effect do thiazide diuretics have, and how does this affect their use?

A

As well as a moderate diuretic effect, thiazides also have an indirect vasodilator action

This is what makes them useful in the treatment of hypertension, and why they are used in combination with other antihypertensive agents to manage blood pressure

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24
Q

Where do thiazide diuretics enter the nephron?

A

They enter in the proximal convoluted tubule because they are protein-bound and cannot pass through at the glomerulus

This also means that their absorption into the tubule is dependent upon the GFR - if GFR is low, less of the drug will be taken up into the tubule

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25
Q

What are some of the adverse effects of thiazide diuretics?

A

Hypokalaemia

Metabolic alkalosis

Hyperuricaemia - may predispose to development of gout

Male sexual dysfunction

Impaired glucose tolerance

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26
Q

How do thiazides relate to stone formation?

A

They can be used in the treatment of renal stone disease as they reduce urinary excretion of Ca2+

This does however make patients more susceptible to developing gout

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27
Q

ADH acts to (increase/decrease) the number of aquaporins in the cell membrane

A

increases the number of aquaporins at the cell membrane

28
Q

Name some proliferative types of glomerulonephritis

A

IgA Nephropathy

Post-infectious GN

Membranoproliferative

Rapidly Progressive GN

29
Q

Name some non-proliferative types of glomerulonephritis

A

Membranous

Minimal Change Disease

Focal Segmental Glomerulosclerosis

30
Q

Carbonic anhydrase inhibitors are largely no longer in use as diuretic agents, but are still used in certain circumstances - what are these?

A

Used to treat glaucoma by lowering intraocular pressure

Used as a prophylaxis for altitiude sickness

Used to treat some forms of infantile epilepsy

31
Q

What is the term used for inflammation of the bladder (either due to infection or other cause)?

A

Cystitis

32
Q

What is a “complicated UTI”?

A

A UTI becomes complicated in the event of systemic symptoms or urinary tract abnormality/obstruction e.g. stones

33
Q

What are some of the risk factors for developing a UTI?

A

Female

  • Shorter, wider urethra
  • Proximity of urethra to anus
  • Increased risk with sexual activity and pregnancy

Catheterised patients

Abnormalities of the urinary tract

34
Q

What are the two routes of infection that could potentially result in a UTI?

Which is more common?

A

Ascending infection from the bladder (more common)

Haematogenous spread (uncommon)

35
Q

What is the best way to test urine for bacteria?

A

Culture

Urine dipsticks might tell you an infection is present but aren’t useful for determining causative organism

36
Q

Gram negative bacteria causing UTIs are (rods/cocci)

These organisms are all (aerobic/anaerobic) and can be further classified based on their ability to _____

Name the organisms that can potentially cause a UTI (9)

A

Gram negative rods

These organisms are all aerobic and can be further classified based on their ability to ferment lactose

Lactose fermenters

  • E coli
  • Klebsiella
  • Enterobacter
  • Serratia
  • Citrobacter

Lactose non-fermenters

  • Oxidase-positive
    • Pseudomonas aeruginosa
  • Oxidase negative
    • Morganella
    • Proteus
    • Providencia
37
Q

What feature of E. coli results in them causing a fever in patients?

A

E. coli posseses an endotoxin in its LPS layer

38
Q

What is Pseudomonas aeruginosa particularly associated with, and what is the treatment?

A

P. aeruginosa is associated with catheters and instrumentation,

and it tends to be resistant to most oral antibiotics except Ciprofloxacin

39
Q

What gram positive organisms can cause UTIs?

A

Enterococcus

  • E. faecalis - more common and less resistant of the two
  • E. faecium

Staphylococcus

  • S. sasphrophyticus
  • S. aureus (uncommon)
40
Q

UTIs - signs and symptoms

A

Dysuria (pain on passing urine)

Frequency

Nocturia

Haematuria (not typically but can occur)

Fever

Loin pain

Rigors

41
Q

How is a urine sample best collected?

A

First urine passed is most likely contaminated and will present with bacteria that are not the causative organism of infection

Best approach is collecting midstream urine

42
Q

If taking a urine sample and using a universal sterile container, within what time frame must it get to the laboratory?

If likely to take longer, what else can be used to contain the specimen? How long can it be stored here?

A

If being kept in a universal sterile container (white cap), a urine sample must make it to the lab within 2 hours

Alternatively, a Boricon container can be used which contains boric acid that will prevent bacteria from multiplying. This can be used to store specimens for around 24 hours

43
Q

Urine dipstick isn’t great for identifying infection in patients. What does it pick up that might indicate infection?

A

Leucocyte esterase - indicates WBCs in the blood

Nitrites - indicates the presence of certain bacteria in the urine (mainly coliforms)

Protein and blood (not for the diagnosis of infection)

44
Q

What scoring criteria is used to determine if a patient has a UTI based on their culture?

A

Kass’s Criteria

>105 organisms/ml = significant bacteria, UTI likely

NB - this is referring to pure growth of a single organism, this amount of organisms made up of multiple species is likely not significant

45
Q

In a woman presenting with an uncomplicated lower UTI, how long a course of antibiotics should she be put on?

A

3 days

46
Q

What is the best treatment in a patient presenting with likely abacterial cystitis/urethral syndrome?

What causes this condition?

A

In this case, the patient will have symptoms of a UTI and pus cells will be present in the urine, but not to a signficant degree

Alkanising the urine may be of benefit as it provides symptomatic relief

This presentation may be the early phase of a UTI, may be due to “honeymoon cystitis” or may be due to urethritis caused by gonorrhoeal/chlamydial infection

47
Q

If a patient presents with bacteria in the urine but is asymptomatic (i.e. asymptomatic bacteriuria), how are they best managed?

A

Antibiotic treatment is often not required, especially in the elderly and the condition may recur if an antibiotic is given

The exception to this is in pregnant women - treat all bacteriuria!

48
Q

Why is bacteriuria ALWAYS treated in pregnant women?

What antibiotics are used?

A

All women are screened for bacteriuria at their first antenatal visit

If left untreated, 20-30% will develop pyelonephritis and it could also cause intra-uterine growth retardation or premature birth

If in 1st trimester, give Nitrofurantoin

If in 3rd trimester, give Trimethoprim

Cefalaxin can also be used and is 2nd line treatment

49
Q

Should patients with a catheter and bacteriuria be given antibiotics?

Why?

A

Only if they have presenting symptoms of infection

Giving antibiotics unnecessarily can result in the catheter becoming colonised with increasingly resistant bacteria

50
Q

Nephrotic syndrome - clinical features

A

Oedema

Hypoalbuminaemia

Hyperlipidaemia

Proteinuria

Patients present with swelling (including the face, which is a good indicator of the condition) and may have other constitutional symptoms e.g. fatigue, lethargy etc.

51
Q

Patient presents with symptoms of nephrotic syndrome and you perform a urinalysis which shows +++ proteinuria and no haematuria. What do you do next?

A

Quantify the proteinuria using either a protein:creatinine ratio on a spot urine sample, or a 24 hour urine collection and measure the protein

Also take a blood sample to check renal function (urea, creatinine and electrolytes) and serum albumin

52
Q

What are some of the causes of Nephrotic Syndrome?

A

Primary GN i.e. GN with no obvious underlying cause

Minimal Change Nephropathy and Membranous nephropathy - commonly cause nephrotic syndrome alongside normal renal function and blood pressure

Glomerular disease associated with an underlying disorder e.g. diabetes, hypertension, SLE, chronic infections etc.

GN associated with drugs - gold, penacillin, antibiotics, NSAIDs etc.

53
Q

Prior to performing a renal biopsy, what procedures must be done first? What contraindications are being screened for?

A

Blood count and coagulation screen - both moderate/severe thrombocytopaenia and coagulation defects are contraindications to renal biopsy

Renal USS - to check size, number and position of kidneys

54
Q

What presentations of kidneys on renal USS would prevent you from performing a renal biopsy?

A

Small kidneys - increased risk of bleeding and likely poor results of biopsy

Presence of a single kidney - relative risk increases

55
Q

Minimal Change Nephropathy - management

A

Steroids - Prednisolone 40-60 mg/day

PPI to protect against peptic ulceration

Prognosis is good and kidney function is not expected to deteriorate.

56
Q

Female with a lower UTI - treatment

A

Trimethoprim or Nitrofurantoin orally for 3 days

57
Q

Uncathaterised male with a UTI - treatment

A

Get cultures!

Trimethoprim or Nitrofurantoin orally for 7 days

58
Q

Complicated UTI or pyelonephritis (GP) - treatment

A

Co-amoxiclav or Co-trimoxazole for 14 days

59
Q

Complicated UTI or pyelonephritis (Hospital) - treatment

A

Amoxicillin and Gentamicin IV for 3 days (replace amoxicillin with co-trimoxazole if allergic)

Step down as guided by antibiotic sensitivities

60
Q

What are some of the considerations that have to be kept in mind when prescribing Gentamicin?

A

It must be given in hospital as it is IV administration only

Avoid in pregnancy

Has a narrow therapeutic index - risk of toxicity and can cause renal problems and issues with CN VIII (balance and hearing loss)

Should be prescribed for 3 days only, unless advised otherwise

61
Q

If bacteria develop beta lactamase, what antibiotics are no longer effective against them?

What antibiotic can be used instead?

A

Bacteria become resistant to all cephalosporins and almost all penicillins

Carbapenems are the only effective treatments against ESBLs (e.g. IV meropenem, IV ertapenem)

Other antibiotics may also be useful - nitrofurantoin (oral), pivmecillinam (oral), temovillin (IV)

62
Q

Typically, first line treatments for coliforms and enterococci are gentamicin and amoxicillin, respectively

What are the second-line drugs used for these organisms?

A

Coliforms

  • Aztreonam
  • Pivmecillinam
  • Temocillin
  • Piperacillin/Tazobactam
  • Meropenem
  • Quinolones
  • Fosfomycin

Enterococci

  • Vancomycin
  • (chloramphenicol)
  • Linezolid
  • (Daptomycin)
  • (Tigocylcine)
63
Q

How does trimethoprim work?

When should it be avoided?

What organisms can it be used to treat, and importantly which one does it not treat?

A

Inhibits bacterial folic acid synthesis

Generally safe antibiotic, but should be avoided in the FIRST trimester of pregnancy

Treats most coliforms, Staph aureus including MRSA but does NOT treat Pseudomonas

64
Q

Why is nitrofurantoin only used to treat lower UTIs?

When should this antibiotic be avoided?

What organisms does it cover and, importantly, what organsism does it not cover?

A

Only useful in uncomplicated lower UTIs as it only reaches effective concentrations in bladder urine

It’s a cheap and narrow spec antibiotic, but should be avoided in the THIRD trimester of pregnancy

Treats most coliforms, Enterococci, Staph aureus including MRSA but does not treat Proteus or Pseudomonas

65
Q

Why is co-amoxiclav more effective against beta-lactamases?

A

The clavulanic acid inhibits beta lactamase

66
Q

How are adverse drug reactions classified (A-F)?

A

A - augmented pharmacological effects

B - bizarre effects

C - chronic

D - delayed

E - end-of-treatment effects

F - failure of therapy

67
Q

What combination of drugs make up the “triple whammy” that particularly predispose the kidneys to developing an AKI?

A

ACE inhibitor/ARB

Diuretic

NSAID