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Phase 2: Reproduction, Nephrology and Urology > PBL 4: Chronic Kidney Disease > Flashcards

PBL 4: Chronic Kidney Disease Flashcards

1
Q

Which nerve innervates the external urethral sphincter?

A

Pudendal nerve

Part of the skeletal motor fibres- voluntarily control

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2
Q

Which nerves innervate the internal urethral sphincter

A

Pelvic splanchnic nerves (parasympathetic innervation)

Hypogastric nerves (sympathetic innervation)

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3
Q

The hypogastric nerve causes the relaxation of the detrusor muscle in the bladder wall – via the stimulation of which receptor, located where?

A

β3-receptors in the fundus and the body of the bladder.

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4
Q

Define micturition

A

Action of urination

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5
Q

What are the two phases of micrturition

A
  1. Storage phase
  2. Voiding phase
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6
Q

Describe the storage phase of micturition

A
  • Urine flows through the ureters into the bladder and enter by the ureteric orifices (located at the trigone region, located posteriorly, of the bladder).
  • Sympathetic innervation (S for storage) causes the relaxation of the detrusor muscle and the contraction of the internal urethral sphincter. This allows the bladder to fill with urine, and allow for it to be stored for many hours.
  • As the bladder fills, the folds in the bladder walls (rugae) flatten and the walls distend, increasing the capacity of the bladder.
  • The bladder fills progressively until the tension in its walls rises above a threshold level eliciting a nervous reflex called the micturition reflex that empties the bladder or, if this fails, at least causes a conscious desire to urinate.
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7
Q

Describe the changes in the transitional epithelium that occurs in the storage phase of micturition

A
  • When the bladder is empty, the transitional epithelium appears cuboidal and the intravesicular pressure is 0.
  • As the bladder fills, the folds in the bladder walls (rugae) flatten and the walls distend
  • In a distended bladder the epithelial cells are stretched and its shape goes from cuboidal to a more squamous.
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8
Q

Describe the receptive relaxation

A

This means that as the bladder fills, it expands, allowing the pressure inside (the intra-vesical pressure) to remain the same and remain lower than urethral pressure – to prevent urine from leaking out

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9
Q

Describe the micturition reflex

A
  • As the bladder fills, many superimposed micturition contractions begin to appear. They are the result of a stretch reflex initiated by sensory stretch receptors in the bladder wall.
  • Stretch reflex: Sensory signals from the bladder stretch receptors are conducted to the sacral segments of the cord through the pelvic nerves and then reflexively back again to the bladder through the parasympathetic nerve fibers by way of these same nerves.
  • When the bladder is only partially filled, these micturition contractions usually relax spontaneously after a fraction of a minute, the detrusor muscles stop contracting, and pressure falls back to the baseline. As the bladder continues to fill, the micturition reflexes become more frequent and cause greater contractions of the detrusor muscle.
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10
Q

Describe the voiding phase of micturition

A
  • Passing of urine is under parasympathetic control.
  • Upon the voluntary decision to urinate, neurones of the pontine micturition centre fire to excite the sacral preganglionic neurones.
  • There is a subsequent parasympathetic stimulation to the pelvic nerve (S2-4) causing a release of ACh, which works on M3 muscarinic ACh receptors on the detrusor muscle, causing it to contract and increase intra-vesicular pressure.
  • The pontine micturition centre also inhibits Onuf’s nucleus, with a resultant reduction in sympathetic stimulation to the internal urethral sphincter causing relaxation.
  • Finally, a conscious reduction in voluntary contraction of the external urethral sphincter from the cerebral cortex allows for distention of the urethra and the passing of urine.
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11
Q

In females, urination is assisted by?

A

Gravity

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12
Q

In males, urination is assisted by?

A

In the male, bulbospongiosus contractions and squeezing along the length of the penis helps to expel all of the urine.

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13
Q

What is the pH range in the blood

A

between pH of 7.35 and 7.45

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14
Q

For every bicarbonate molecule formed how many hydrogen ions are lost?

A

1

+ 1x Bicarbonate = - 1x H+

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15
Q

What are the sources of hydrogen ions?

A
  • H+are produced in the body as a result of metabolism, particularly from the oxidation of the sulphur-containing amino acids of proteins ingested as food
  • Western diet is typically an acid load diet. Contains significant amounts of animal protein (meal). Animal proteins contains sulphur containing amino acids (cysteine and methionine). When the amino acids are metabolised, the sulphur is converted to sulphuric acid (H2SO4) which is then leads to lots of protons being released.
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16
Q

Name the 3 mechanisms in which the body regulated acid-base

A
  1. Buffering
  2. Ventilation
  3. Renal regulation of bicarbonate and hydrogen ion secretion and reabsorption.
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17
Q

Describe the buffering mechanism used to regulate acid-base

A
  • A variety of buffering systems permits blood and other bodily fluids to maintain a narrow pH range. These systems include:
    • Carbonic acid/bicarbonate system (main one)
    • Haemoglobin
    • Protein buffer system- intracellular buffering mechanism
    • Bone- long term buffer and contributes to osteromalacia in chronic acidosis
    • Phosphate
  • A buffer is defined as a chemical system that prevents a radical change in fluid pH by dampening the change in hydrogen ion concentrations in the case of excess acid or base.
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18
Q

Describe how the respiratory tract adjust the pH

A
  • The respiratory tract can adjust the blood pH upward in minutes by exhaling CO2 from the body.

NOTE: CO2 + H2O ↔ H2CO3 ↔ HCO3 + H+

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19
Q

Describe how the renal system adjusts the pH

A

The renal system can also adjust blood pH through the excretion of hydrogen ions (H+) and the conservation of bicarbonate, but this process takes hours to days to have an effect.

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20
Q

Which acid base mechanism adjust blood pH within minutes

A

Respiratory tract

Blowing CO2

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21
Q

Which acid base mechanism takes tours to days to adjust blood pH

A

Renal system

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22
Q

Reabsorption of HCO3 occurs where?

A

The proximal convoluting tubule in the nephron of the kidneys.

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23
Q

Describe the carbonic-acid-bicarbonate system

A

CO2 + H2O ↔ H2CO3 ↔ HCO3 + H+

  • This system is at equilibrium until acid base are no longer in equilibrium.
  • This process is essentially consuming HCO3 or adding HCO3 to prevent H+ from changing.
  • If H+ were added to the system, the addition H+ are consumed by the bicarbonate molecules driving the equation to the left. Resulting in carbon dioxide and water being formed. The excess carbon dioxide is exhaled. As a result, this removes the ion from circulation, preventing the accumulation of acid in the body.
  • This is by far the most important buffer for maintaining acid-base balance in the blood.
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24
Q

What is the most important buffer for maintaining acid-base balance in the blood?

A

Carbonic acid- Bicarbonate system

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25
Q

What are the limiations of the carbonic acid-Bicarbonate system in maintaining acid-base homeostasis

A

Limitation, as there is a limited number of free bicarbonate molecules in the body. The kidneys regulate the level of bicarbonate by reabsorbing from the tubule (linked to the excretion of H+).

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26
Q

Describe the 5 steps of reabsorbing filtered bicarbonate

A

Occurs in the proximal convoluting tubule in the nephron.

  • Step 1: Sodium ions are reabsorbed from the filtrate in exchange for H+ by an antiport mechanism in the apical membranes of cells lining the renal tubule. H+ are now in the proximal tubule lumen.
  • Step 2: The H+ and filtered bicarbonate combine to form carbonic acid (in the lumen of the tubule).
  • Step 3: The carbonic acid is metabolised by carbonic anhydrase into water and carbon dioxide.
  • Step 4: The water and carbon dioxide freely pass into the tubular cell, where it is metabolised by carbonic anhydrase to form H+ and bicarbonate.
  • Step 5: The H+ are exchanged from sodium (Step 1) while the bicarbonate passes into the peritubular capillaries and returns to the blood
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27
Q

Which enzyme metabolises carbonic acid into water and carbon dioxide

A

carbonic anhydrase

28
Q

The carbonic acid-bicarbonate system does not excrete which kind of acid?

A

Fixed acid- an acid produced in the body from sources other than carbon dioxide, and is not excreted by the lungs.

29
Q

Name the two mechanisms used to excrete excess H+

A
  • Titration of filtered PO4
  • Secretion of NH4 into urine
30
Q

Describe the Titration of filtered PO4 process

A
  • Hydrogen ions are actively transported into the lumen via hydrogen-ATPase pumps.
  • Only 85% of the total phosphate is reabsorbed.
  • The left-over phosphate in the lumen can bind to a large portion of hydrogen ions. This buffers the H+ into dihydrogen phosphate.
  • This dihydrogen phosphate is excreted in urine.
31
Q

Describe the NH4 mechanism of extracting excess H+

A
  • Glutamine is converted to glutamate and ammonium (NH4+) in the proximal convoluted tubule (PCT) by glutamase.
    • The glutamate is converted into bicarbonate via the alpha ketoglutarate. This bicarbonate can be reabsorbed to further increase pH.
  • The NH4+ is excreted into the lumen of the tubule in exchange to Na+. Here it dissociates into ammonia and hydrogen ions.
  • Once in the lumen, the ammonia reforms into ammonium by picking up a luminal hydrogen ion, allowing hydrogen to be excreted as ammonium.
32
Q

Where does glutamine come from

A

Glutamine comes mainly from the metabolism of amino acids in the liver.

33
Q

Glutamine is converted to glutamate and ammonium (NH4+) in the proximal convoluted tubule (PCT) by which enzyme

A

Glutamase

34
Q

The glutamate is converted into bicarbonate by which enzyme

A

alpha ketoglutarate

35
Q

Define chronic kidney disease

A

The presence of kidney damage or decreased kidney function that persists for at least 3 months i.e. a chronic reduction in kidney function. This reduction in kidney function tends to be permanent and progressive

Leads to irreversible loss of nephrons

36
Q

What is the most common cause of chronic kidney disease

A

Diabetes mellitus

37
Q

What is the second most common cause of chronic kidney disease

A

Hypertension

38
Q

Name some causes of chronic kidney disease

A
  • Metabolic disorders
    • Diabetes mellitus
    • Obesity
  • Hypertension
  • Age related decline
  • Immunological disorders
    • Glomerulonephritis- inflammation of the glomerulus
  • Congenital disorders
    • Polycystic kidney disease
  • Medications
    • NSAIDS, PPIs, lithium
39
Q

What are the signs and symptoms associated with chronic kidney disease

A
  • Early stages of CKD are usually asymptomatic
  • Often only diagnosed on routine testing
  • Later stages may cause the following symptoms:
    • Fatigue (as a result of anemia, which is due to the lack of erythropoietin produced by the kidney)
    • Loss of appetite
    • Oedema (result of salt and water retention due to reduce GFR)
    • Muscle cramps
    • Haematuria
    • Pruritus (itching)
40
Q

Describe the pathogenesis of chronic kidney disease

A
  • Many factors can cause injury to the nephrons, e.g. hypertension, which if chronically leads to the loss of these nephrons
  • The loss of nephrons leads to glomerular hyperfiltration, where the blood flow is redirected to the healthy nephrons.
  • Initially, you get a rise in GFR in these healthy nephrons.
  • After a while, the hyperfiltration results in sclerosis, which will eventually lead to the loss of these nephrons.
  • The cycle will continue and will eventually leads to a reduction in GFR.
41
Q

What investigations would you do in chronic kidney disease

A
  • Serum creatinine - Determine abnormality of the GFR
  • Urinalysis - Checking the appearance, concentration and content of urine
  • Urine micralbumin - If microalbumin is present, it is a risk factor for CKD. Not detected in dipstick test.
  • Renal ultrasound - imaging the kidneys to detect atrophy or/and presence of kidney stones. To rule out.
42
Q

What are the two scoring systems used in diagnosing chronic kidney disease

A

A score - is based on the albumin:creatinine ratio (better score the closer the ratio is to zero because there should be no protein in the urine with high levels of creatinine in the urine).

G score - based on eGFR.

43
Q

What is the treatments options for chronic kidney disease

A
  • CKD is irreversible- can only be managed.
  • Aim is to slow down the rate of kidney damage and treat risk factors
  • Lifestyle changes – to help you stay as healthy as possible
  • Medicine – to control associated problems, such as high blood pressure and high cholesterol
  • Dialysis– treatment to replicate some of the kidney’s functions, which may be necessary in advanced (stage 5) CKD
  • Kidney transplant– this may also be necessary in advanced (stage 5) CKD
44
Q

What are the 1st line medications used to manage chronic kidney disease

A

ACE inhibitors or angiotensin 2 receptor antagonist AND Statin

  • Hypertension is one of the greatest risk factors for the progression of CKD, regardless of aetiology.
45
Q

What is the 2nd line medications used to manage chronic kidney disease

A

Additional hypertensive therapy

46
Q

What is the 3rd line medications used to manage chronic kidney disease

A

non-dihydropyridine calcium-channel blockers WITH statin

calcium blockers e.g. Amlodipine

Statin e.g. Atorvastatin

47
Q

What additional therapies may be required in patients with chronic kidney disease

A
  • Anemia: addition of erythropoietin-stimulating agents
  • Secondary hyperparathyroidism (as the kidneys cannot make enough vitamin D to absorb calcium resulting in low blood calcium levels- as a result more PTH is released causing hypertrophy of the parathyroid gland) : Dietary modifications
  • Metabolic acidosis: Oral sodium bicarbonate
48
Q

What are the treatment options for patients with end stage renal failure

A
  • Dialysis
  • Kidney transplant
49
Q

____ endogenous are excreted by the renal system.

A

Hydrophilic

50
Q

What is the function of diuretic drugs

A

They increase the excretion of Na+ and water by decreasing the reabsorption of Na+ and (usually) Cl− from the filtrate, increased water loss being secondary to the increased excretion of NaCl (natriuresis).

51
Q

What are the 3 major types of diuretics

A

Loop diuretics

Thiazides

Potassium-sparing diuretics

52
Q

Describe the loop diuretics

A
  • LD are the most powerful diuretics
  • Capable of causing the excretion of 15–25% of filtered Na+
  • The main example is furosemide
  • These drugs act on the thick ascending limb, inhibiting the Na+/K+/2Cl− carrier in the luminal membrane by combining with its Cl− binding site.
53
Q

Which type of diuretic is the most powerful?

A

Loop diuretics

54
Q

Give an example of a loop diuretic

A

Furosemide

55
Q

Describe thiazides

A
  • These are diuretics that act on the distal tubule to cause sodium and water loss.
  • Better tolerated than loop diuretics
  • They bind to the Cl− site of the distal tubular Na+/Cl− co-transport system
  • Hence decreasing the release of sodium into the lumen of the tubule. Preventing excretion.
56
Q

When is thiazides preferred?

A

Preferred in treating uncomplicated hypertension

57
Q

Give an example of a thiazide

A

Bendroflumethiazide

58
Q

Describe the potassium-sparing diuretics

A
  • Very limited diuretic action when used singly, because distal Na+/K+ exchange—the site on which they act accounts for reabsorption of only 2% of filtered Na+
  • Main example is spironolactone
  • They can prevent hypokalaemia (low potassium levels) when combined with loop diuretics or with thiazides
  • They compete with aldosterone for its intracellular receptor thereby inhibiting distal Na+ retention and K+ secretion
59
Q

Give an example of a potassium-sparing diuretic

A

Spironolactone

60
Q

Which diruetic works by inhibiting the Na+/K+/2Cl− carrier

A

Loop diuretics

61
Q

Which diuretic works by binding to the Na+/Cl− co-transport system preventing the co-transporter from working

A

Thiazdes

62
Q

Which diuretic competes with aldsterone hence inhibiting sodium retention and potassium secretion

A

Potassium-sparing diuretics

63
Q

Which diuretic acts of the loop of Henle? which limb does it effect

A

Loop diuretics

Thick ascending limb

64
Q

Which diuretic acts on the distal tubule of the nephron

A

Thiazides

Potassium-sparing diuretics

65
Q

Name these diuretics

A

Phase 2: Reproduction, Nephrology and Urology (25 decks)

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