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Foundations 3 > RENAL PHYSIOLOGY > Flashcards

RENAL PHYSIOLOGY Flashcards

1
Q

What are the roles of the kidney?

A
  • Elimination of endogenous and exogenous compounds
  • Maintenance of chemical homeostasis
  • Maintenance of volume status
  • Endocrine signalling
  • Bladder needed to store urine and detrusor muscle around it maintain continence
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2
Q

What has the greatest independent control in order to maintain water body body?

A

Urine

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3
Q

What are components that make up extracellular compartment?

A
  • Plasma
  • Interstitial fluid
  • Transcellular: Separated by extracellular by a membrane eg. CSF, peritoneal space, sinovial fluid, pleural cavity
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4
Q

How can one measure body fluid compartments?

A

Injecting a substance that is known to distribute in a given compartment and then calculate the volume of distribution. Vd = Q (amount of drug)/ Plasma concentration of drug

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5
Q

Total body fluid is 42L. What is the estimated volume for each compartment?

A 
Extracellular: 14L
- Plasma 3.5L
- Interstitial fluid 10L
- Transcellular fluid 1L
Intracellular: 28L
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6
Q

What is the volume of distribution for heparin which is confined to the plasma?

A

3.5L

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7
Q

What can be used to label water?

A

Instead of 1H use deuterium or tritium

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8
Q

What is the extracellular and intracellular concentration values for the following ions?

a) Sodium
b) Potassium
c) Bicarbonate
d) Glucose (fasting)
e) Osmolality

A

a) i. 140mM ii. 15mM
b) i. 4mM ii. 140mM
C) i.25mM ii. 12mM
d) 4mM
e) 285mOsm/kg

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9
Q

For calcium, what is the proportion of free calcium ions? Which calcium is calculated clinically?

A

1/2 of extracellular calcium the rest are bound to plasma protein -albumin. In clinical practice, total calcium is measured so a correction equation is used. Calcium corrected = Calcium total +0.020 (40-albumin)

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10
Q

What is an osmole?

A

Number of molecules that a compound dissociates into when dissolved in solution. Eg 100mmol of NaCl yields 200mOsm because it dissociates into two ions.

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11
Q

Difference between osmolality and osmolarity?

A

Osmolality is the number of osmoles per unit mass of solvent.
Osmolarity is the number of osmoles per unit volume of the solution

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12
Q

What is an osmotic pressure?

A

Force per unit area required to oppose hydrostatic pressure which allows movement of molecules from one side to another.

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13
Q

What can cause a fall in albumin?

A

Liver and renal failure

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14
Q

What are the effects of a fall in albumin and why?

A

When there is decreased albumin, filtration will be higher as Pcap -oncotic pressure of capillary (decreases). This can lead to pulmonary/peripheral oedema and ascites

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15
Q

How can oedema due to a low albumin levels be corrected?

A

Mannitol can be used to increase plasma and extracellular space osmolality as it is a stable sugar alcohol. Increases reabsorption of fluid.

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16
Q

uses of mannitol

A
  1. To combat raised intracranial pressure due to intracranial haemorrhage.
  2. Used as an osmotic diuretic
  3. Modern use: Inhalation for cystic fibrosis management
  4. Used to check if renal system works after transplantation
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17
Q

Difference between isotonic and isosmotic

A

Isotonic: No nett flow of fluid.
Isosmotic: Same osmolality but eg urea because there is a transporter it will allow urea to pass through and that will result in a nett flow of water which makes urea an ineffective osmolyte

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18
Q

What is the functional unit of the kidney?

A

Nephron

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19
Q

What is the renal plasma flow rate?

A

600ml/min

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20
Q

Where does filtration occur in the kidney?

A

Glomerulus

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21
Q

Starling’s forces required to cause filtration so what are they?

A

Capillary hydrostatic and oncotic pressure

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22
Q

What happens to oncotic pressure along the length of the capillaries?

A

It increases as filtration occurs, there concentration of protein increases however they never reach equilibrium in healthy people

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23
Q

What is the hydrostatic pressure in the glomerulus compared to capillaries?

A

50mmHg arterial hydrostatic pressure in the glomerulus but about 35mmHg in other capillaries

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24
Q

What are the 2 ways you can increase glomerular hydrostatic pressure?

A
  1. Afferent vasodilation

2. Efferent vasoconstriction

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25
Q

What affects the driving force?

A

The osmotic pressure of the proteins

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26
Q

Osmotic pressure calculation

A

Osmotic pressure = nCRT
nC= Osmolality
R= Ideal gas constant
T = Temperature

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27
Q

Where does the efferent capillary go after leaving the glomerulus? What is the difference in the hydrostatic and oncotic pressures in this capillary bed compared to the rest?

A

Enters a portal vein system that travels to a second capillary bed surrounding the Loop of Henle. Hydrostatic pressure is similar to capillary but very high oncotic pressure –> Reduced filtration, increased reabsorption

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28
Q

What are the 3 barriers for glomerular diffusion?

A
  • Endothelial cells of the glomerular capillaries which are fenestrated 60nm holes and have glycocalyx which repel negatively charged proteins.
  • Glomerular basement membrane also has negatively charged protein like collagen.
  • Epithelial cells of Bowman’s capsule (Podocytes); have pedicels which interdigitate with their neighbours and form another barrier to the movement of fluid
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29
Q

Criteria needed for molecule to pass through glomerulus to become a filtrate?

A
  • Size needs to be <10kDa

- Larger molecules found if positively charged and if due to damage, glomerulus becomes more leaky

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30
Q

What is the typical GFR rate?

A

120ml/min

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31
Q

What is the use of the hydrostatic pressure of 10mmHg in the Bowman’s capsule?

A

To drive fluid through the rest of the nephron

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32
Q

What is a filtration fraction?

A

Proportion of plasma flow filtered by the glomerulus. GFR/Renal flow rate

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33
Q

How should the molecule needed to calculate GFR be like?

A

It has to be produced at a constant rate, not reabsorbed or secreted along the tubules. Eg. Creatinine (derived from creatine phosphate)

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34
Q

Calculating GFR using creatinine

A

GFR x Conc of creatinine in plasma = Conc of creatinine in urine x V dot rate of production of urine
GFR = Conc of creatinine in urine xV dot/ (Conc of creatinine in plasma)

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35
Q

On what basis is GFR estimated?

A

Creatinine is produced at a constant rate so at equilibrium rate of production = rate of excretion by the kidney = GFRx Creatinine conc in plasma so GFR inversely proportional to creatinine conc in plasma.

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36
Q

What happens to GFR as we age?

A

GFR decreases as we progressively lose nephrons and this causes creatinine to rise but equation for eGFR shows that rate of creatinine production falls with age. However, normal loss of renal function with age will place a limit on longevity if no other reason for death.

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37
Q

What does proteinuria suggest?

A

Glomerular dysfunction

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38
Q

What can cause glomerular dysfunction?

A
  1. Nephrotic syndrome
  2. Glomerulonephritis
  3. Congenital nephrotic syndrome - affects podocytes of the epithelial membrane of Bowman’s capsule which makes glomerulus more permeable to plasma proteins.
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39
Q

What are the 2 parts to proximal tubule of a nephron

A
  1. Proximal convoluted tubule

2. Proximal straight tubule

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40
Q

Which part of the kidney is the proximal tubule found in?

A

The cortex

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41
Q

What are the 2 methods in which ions can move?

A
  1. Transcellular - through the cell
  2. Paracellular - between cells
    By the end of proximal tubule, 70% of water reabsorbed
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42
Q

Explain the appearance of the proximal tubular cells

A

There have microvilli forming the brush border to increase the surface area

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43
Q

How does water move in the proximal tubule?

A

Via aquaporin-1. They are present on both the apical and basolateral surface of the proximal tubule.

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44
Q

Explain the process of glucose reabsorption.

A

Na+/K+ ATPase pump sets up an electrochemical gradient so secondary co-transporter of glucose with sodium entry occurs. In the early part, SGLT-2 (apical) reabsorbed from the filtrate and GLUT-2 (basolateral) reabsorbs it into cortical interstitial space. In the late part, SGLT-1 (apical) and GLUT-1 (basolateral) used but same reabsorption process occurs.

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45
Q

Is there a tubular maximum transport for glucose?

A

Yes at 380mg/min is more than that glucose will be excreted in the urine.

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46
Q

What is the difference between SGLT-2/1?

A

SGLT-2 is high capacity and low affinity whereas SGLT-1 is low capacity and high affinity so found towards the later end of the proximal tubule

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47
Q

What is the function of SGLT-2 inhibitors?

A

Prevents the reabsorption of glucose so increased elimination. This will help reduce blood glucose levels in those with hyperglycaemia.

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48
Q

What side effects seen with SGLT-2 inhibitors?

A

Drop in glucose can result in decreased energy levels, fatigue, diabetic ketoacidosis, nausea, dry mouth and thirst

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49
Q

How are amino acids transported in the proximal tubule?

Normal concentration of amino acid is 2.5-3.5mM

A

Via co-transport sodium channels. It is tubular maximum limited.

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50
Q

Explain the process of HCO3- reabsorption. Concentration of HCO3- in the filtrate in 25mM.

A
  1. In the cell, carbonic anhydrase converts CO2 and H2O that diffused into the cell from the filtrate into hydrogen ion and bicarbonate ion.
  2. H+ transported into filtrate via Na+/H+ antiport whereas Bicarbonate/chloride antiport transports bicarbonate into the filtrate.
  3. Bicarbonate from the cell is also reabsorbed via 3Bircarbonate/Na co-transporter at the basolateral membrane.
  4. In the filtrate, Carbonic Anhydrase re-converts them both back into water and carbon dioxide.
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51
Q

Where are the carbonic anhydrase located at?

A
  1. Brush border

2. In the cell

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52
Q

What is the function of acetazolamide in the proximal tubule and what is it used for in clinical practice?

A
  • Acts mostly in the proximal tubule to inhibit carbonic anhydrase.
  • Weak diuretic; Increase bicarbonate excretion so urine becomes alkaline whereas metabolic acidosis occurs.
  • Used in glaucoma and mountain sickness prophylaxis
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53
Q

How does Cl- move in the proximal tubule?

A
  1. Actively via HCO3-/ Cl- antiporter but not needed as much because absorption of bicarbonate balanced by sodium uptake. 3HCO3-/Na+ at basolateral membrane.
  2. Passively: As water moves due to bicarbonate reabsorption, Cl- concentration increases so then moves paracellularly down its concentration gradient at the end of proximal tubule
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54
Q

What happens to albumin?

A

Very little enters filtrate at the glomerulus but those that do enter degrade into amino acids and reabsorbed via amino acid/Na+ co-transporter.

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55
Q

How does active secretion in the proximal tubule occur?

A
  1. PAH- (ex of an organic anion that is secreted in the proximal tubule) enters the cell via OAT (Organic Anion Transporter). It is exchanged with aKG2- that comes into cell via co-transporter sodium.
  2. PAH- then enters filtrate via MRP (multidrug resistance-associated protein) in exchange of a anion such as chloride, bicarbonate, hydroxide.
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56
Q

What are the ways in which sodium can enter from filtrate to cell?

A
  1. Na+/glucose
  2. Na+/H+ antiport
  3. Na+/amino acids
  4. ENac channel which plays a minor role in early proximal and more dominant in the late proximal tubule via secondary active transport.
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57
Q

What are the two functionally distinct components of the Loop of Henle?

A
  1. Thick Ascending limb

2. Descending Limb

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58
Q

Where is the Loop of Henle in the kidney?

A

It is in the outer and inner medulla.

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59
Q

What is the key function of the thick ascending limb?

A

To create a hyperosmolar interstitial space in the medulla to drive water loss from the descending limb and collecting duct.

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60
Q

What happens to water in the descending limb?

A

Permeable to water so water leaves the filtrate into interstitial space because of osmotic force.

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61
Q

What is the osmotic gradient that TAL can sustain?

A

200mOsm/kg

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62
Q

How does TAL cause a hyperosmolar environment to be created?

A
  1. Na+/K+ ATPase pump on the basolateral surface of the cell which causes an electrochemical gradient to be created.
  2. NKCC2 transporter allows movement of 1 Na+, 1K+ and 2 Cl- ions to enter from the filtrate into the cell.
  3. K+ recycled through the apical membrane via transporter ROMK ensures that transporter can maintain its role of transporting large quantities of sodium/chloride. Also it creates a positive charge for calcium and magnesium reabsorption.
  4. K+/Cl- also re-absorbed into interstitium via transporters.
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63
Q

What family does NKCC2 transporter belong to?

A

Member of SLC12 family of cation coupled chloride transporters.

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64
Q

How does furosemide act as a diuretic?

A
  • It is a loop diuretic which acts on the TAL.
  • Inhibits the NKCC2 transporter so allows 20% of filtered sodium to be excreted.
  • Can cause natriuresis (excretion of sodium) and diuresis (excess urine)
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65
Q

When is furosemide used?

A

Cardiac and renal failure

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66
Q

What are the side effects of furosemide?

A
  • Loss of K+ ions which could lead to hypokalaemia which can lead to cardiac dysrhythmia.
  • Especially if prescribed with digoxin (Na+/K+ ATPase pump inhibitor)
  • Hypovolaemia due to diuresis
  • Mild metabolic alkalosis due to distal Na+/H+ exchanger
  • Loss of Magnesium and calcium
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67
Q

What happens to the osmolality as down the descending limb?

A

Osmolality can increase up to 1200 mOsm/kg due to extraction of water.

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68
Q

What happens to osmolality up the TAL?

A

Osmolality decreases due to extraction of ions.

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69
Q

What is the benefit of countercurrent multiplier mechanism in the Loop of Henle?

A

93% of ions can be reabsorbed using a transporter system that can maintain a 200mOsm difference.

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70
Q

Explain the reabsorption of ions in the distal convoluted tubule.

A
  1. Na+/K+ ATPase pump that creates an electrochemical gradient.
  2. Na+/Cl- co-transporter on the apical membrane allows the entry of these ions into the cell.
  3. There’s a K+/Cl- co-transporter in the basolateral membrane which causes reabsorption of potassium and chloride.
  4. There is also a PTH receptor on the cell. When stimulated allows calcium entry from the filtrate via apical membrane into the interstitium (reabsorption) via the Na+/Ca2+ antiporter.
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71
Q

What is the function of thiazide or thiazide-like drugs?

A
  • Blocks the Na/Cl- co-transporter in the distal convoluted tubule.
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72
Q

What is the use of thiazide?

A

Antihypertensive and diuretic used alongside furosemide.

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73
Q

What are the side effects of thiazide?

A
  • Increased uric acid.
  • Hyperglycaemia
  • Hyponatraemia
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74
Q

How is water transported in the collecting ducts?

A

Aquaporin 2 on the apical side and Aquaporin 3 on the basolateral side. ADH stimulates the increase in the insertion of these channels via Gs.

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75
Q

How are Na+/K+ reabsorbed in the collecting duct.

A
  1. Na+/K+ ATPase pump sets up an electrochemical gradient.
  2. Na+ enters the cell from the filtrate via ENac channels on the apical side.
  3. K+ uses a ROMK to enter into filtrate to be excreted.
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76
Q

What is the function of aldosterone?

A

Aldosterone stimulates the upregulation of ENac channel and Na+/K+ ATPase channel. It increases the excretion of K+ and reabsorption of Sodium.

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77
Q

What is the function of spironolactone and give and example of it?

A

Inhibits the effect of aldosterone on the ENac. Increases the excretion of sodium and water but no effect on potassium.
Ex: Amiloride

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78
Q

In what condition is spironolactone used?

A

Used in heart failure so that it can be potassium sparing and it is a moderately effective diuretic.

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79
Q

What are the other side effects of spironolactone?

A
  • Gynaecomastia
  • Menstrual disorders
  • Testicular hypertrophy
  • Hyperkalaemia
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80
Q

Explain transport process of urea throughout the nephron.

A
  1. Glomerulus - Urea is 100% filtered so enters Bowman’s capsule.
  2. Proximal convoluted tubule - 50% of urea reabsorbed passively.
  3. Loop of Henle Descending Limb - Concentration of urea increases due to extraction of water.
  4. Distal tubule - Concentration of urea continued to increase however impermeable to urea.
  5. Medullary collecting duct - Permeable to urea so diffusion into the interstitium occurs via UT-A1 transporter.
  6. Increased in urea concentration in interstitium results in high osmotic pressure in the medulla which will allow it to re-enter the descending limb via UT-A2 transporter.
  7. This increases osmolality in the descending limb so greater reabsoprtion of water.
  8. Urea also gets reabsorbed into the vasa recta.
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81
Q

What controls the expression of UT-A1 transporter?

A

ADH

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82
Q

What happens to flow rate along the nephron?

A

Flow rate along the nephron decreases due to extraction of water.

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83
Q

What regulates the urine osmolality and flow?

A

ADH

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84
Q

Where is the ADH synthesised and releases?

A

Synthesised in the hypothalamus then enters into posterior pituitary via hypophyseal portal system then released.

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85
Q

Where does the ADH act on and what does it do?

A

Acts on the distal tubule and collecting duct. Increases water permeability by increasing AQP2.

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86
Q

What are the cellular pathways regulating AQP2 on the apical membrane.

A
  1. ADH binds to the V2 receptor. When stimulated, via Gs produces cAMP.
  2. cAMP stimulates nucleus transcription which synthesis AQP2 .
  3. cAMP then stimulates PKA which aids in the insertion of AQP2.
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87
Q

What happens to the osmolality and flow rate in the nephron when there is no ADH?

A

Cannot have a greater extraction of water in the collecting tubules so osmolality not very high (about 60mOsm/kg) whereas the flow rate is higher than normal because more fluid present.

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88
Q

What happens to the osmolality and flow rate in the nephron when there is a maximum ADH?

A

Maximum extraction of water in the collecting duct which would contribute to very high osmolality in the urine about 1400mOsm/kg and flow rate is very low

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89
Q

What is the similarity between AQP2 and UTA1?

A

Their synthesis are both regulated by ADH.

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90
Q

What happens when there is a presence of selective protein starvation?

A
  • Urea production is lower

- Capacity for urine to be concentrated is lower.

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91
Q

How do cells in the medulla survive if the osmolality is about 1200mOsm/kg?

A

There is an accumulation of a range of organic osmolytes within the cells which include sorbitol, inositol.

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92
Q

What are the 2 types of diabetes insipidus?

A
  1. Central Diabetes Insipidus

2. Nephrogenic Diabetes Insipidus

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93
Q

What are the signs of diabetes insipidus?

A
  • Polyuria
  • Dehydration could lead to polydipsia
  • Hypovolamia
  • Hypernatraemia if fluid intake is inadequate.
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94
Q

What are the causes for central diabetes insipidus?

A

Head injury, tumour, infection

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95
Q

How does one manage central diabetes insipidus?

A
  • ADH analogue such as desmopressin.
  • Thiazide diuretic which acts on the Na/Cl transporter in the distal tubule offers protection against hypernatraemia.
  • It also seems to offer increased water reabsorption in the proximal tubule.
  • Increased aquaporin expression.
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96
Q

What are the causes of nephrogenic diabetes insipidus?

A
  • Lithium toxicity (drug used in bipolar syndrome)
  • Hypercalcaemia
  • Genetic due to mutations either in V2 or AQP2.
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97
Q

What are the treatments for Nephrogenic Diabetes Insipidus?

A
  • Thiazide diuretic to prevent hypernatraemia

- Low salt diet

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98
Q

What is SIADH and cause of it?

A

Syndromes of Inappropriate ADH. Very high ADH probably due to a head injury

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99
Q

What are the symptoms of SIADH in terms of urine and sodium levels?

A
  • Very concentrated urine

- Hyponatraemia

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100
Q

What are the treatments available SIADH

A
  • Fluid restriction

- Give urea

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101
Q

What is the path of the vasa recta?

A

Formed from the efferent arterioles from the glomerulus which run into portal vessels which plunge from cortex into deep medulla forming a hairpin loop like the Loop of Henle.

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102
Q

What is the function of the vasa recta?

A
  • Uptake of water and solvents from the interstitial space after absorption.
  • Transport substances into the interstitial spaces so that it can be secreted into the tubules.
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103
Q

How does the vasa recta affect and why it has this effect?

i. Ascending limb
ii. Descending limb

A

Vasa recta capillaries are permeable so they osmotic pressure changes based on the local interstitial pressure.

i. Ascending limb - Low osmotic pressure concentrating the interstitium in the ascending limb.
ii. Descending limb - High osmotic pressure so dilutes the interstitium on the descending limb

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104
Q

What is the difference in flow rate between ascending and descending limb?

A

Ascending limb flow rate increases as the water enters whereas in descending limb flow rate decreases as water leaves.

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105
Q

What are the 2 mechanisms for renal blood flow autoregulation?

A
  1. Myogenic autoregulation
  2. Tubuloglomerular reflex: regulate single nephron GFR which would affect renal blood flow if many nephrons are affected.
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106
Q

What is the autoregulatory range of the kidneys?

A

80-180 mm/Hg

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107
Q

How a myogenic response occurs?

A

Increase in perfusion pressure causes the afferent arterioles to contract to cause vasoconstriction. This increases resistance and thus reduces flow rate. (Poiseuille’s Law).

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108
Q

Myogenic response measured quantitatively:

A

If change in pressure is (1+x) then change in r^4 will be 1/(1+x). So change in r = (1+x)^-0.25. For small x change is approx (1-0.25x)

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109
Q

What is the cellular mechanism of stretch activated receptors?

A

Stretch activated cation receptors depolarise to cause calcium influx which results in contraction.

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110
Q

How does the tubuloglomerular feedback work?

A

High sodium levels in the distal tubule detected by macula densa. ATP released that is broken down to adenosine which causes vasoconstriction of afferent arterioles. This leads to a fall in flow rate so fall in GFR.

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111
Q

What factors oppose renal autoregulation of blood flow?

A
  1. Circulating hormones

2. Renal innervation

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112
Q

What innervates the renal vasculature?

A

Mostly sympathetic nerves that release noradrenaline to cause vasoconstriction when there is a fall in blood pressure. This reduces renal blood flow so that volume can be retained and oxygen can be maintained.

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113
Q

What circulating hormones affect the renal vasculature?

A

Adrenaline which acts on A1 for smooth muscles and B1 for granule cells. Vasoconstrictor for A1 and vasodilator for B1.

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114
Q

How is the renal plasma flow measured and what characteristics does the compound need to possess?

A

Compound needs to be completely removed from the plasma and completely lost in the urine. Secretion rate should equate to rate at which compound leaves the kidney. PAH (organic anion used).
RPF= Concentration of PAH in urine x V dot rate of urine flow/ (Concentration of PAH in plasma)

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115
Q

What is clearance?

A

Volume of body fluid cleared of a substance per unit of time.

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116
Q

Calculation of clearance.

A

Clearance = Concentration of drug in urine x Urine Flow rate/ (Concentration of drug in plasma)

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117
Q

If renal clearance is 0

A

It was not filtered or secreted so could be a large protein.

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118
Q

If renal clearance <120

A

It is filtered and partially reabsorbed

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119
Q

If renal clearance =GFR

A

It is filtered but not reabsorbed

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120
Q

If renal clearance >GFR but < RBF

A

Filtered, partially secreted

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121
Q

=RPF

A

Filtered and secreted

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122
Q

> RPF

A

Production in the kidney

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123
Q

What is used in clinical practice to measure GFR? How is it given? What properties does it have?

A

Inulin is injected intravenously and clearance rate is measured.
Small enough to pass through glomerulus, not secreted or absorbed throughout the nephron.
Clearance= GFR

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124
Q

What is the normal filtration fraction in a healthy young man?

A

(120/600)x100%= 20%

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125
Q

How to measure half life of a drug?

A

T(1/2) = ln2/k

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126
Q

What is the relationship between k, Vd and Clearance

A

Clearance=k x Vd

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127
Q

If asked to measure proportion of drug after a certain period of time?

A

N= No e^-kt

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128
Q

How would overdose management differ between a young, healthy person compared to someone with renal failure?

A
  • In a young person, renal clearance is efficient so although they start with a x times more than usual eventually there will not be a difference between overdose and not, if no dose skipped.
  • In renal failure patient, clearance is poorer so slow decline of drug and thus takes a longer time to reach normal resting values so doses should be skipped.
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129
Q 
What are the estimated fluid values for the below?
1. Drinking
2. Food
3. Metabolism
4. Respiration
5. Skin- insensible perspiration
6. Urine 
7. Sweating
Which of these are intake and losses?
A
  1. 1.5L
  2. 0.5L
  3. 0.4L
  4. 0.4L
  5. 0.4L
  6. 1.5L
  7. 4.0L
    Intake: Drinking, food, metabolism
    Losses: Respiration, insensible perspiration, urine
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130
Q

Where is change in osmolality detected and what is special about this region?

A

AV3V- Atrioventral 3rd ventricle.

BBB is incomplete in this region

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131
Q

What is the pathway of signalling to produce ADH and when is it produced?

A

Increased in osmolality detected by AV3V region and neurones project towards supraoptic and paraventricular nuclei of the hypothalamus where ADH is synthesised as a prehormone. It enters the hypophyseal portal system where it is cleaved to then be released from the posterior pituitary.

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132
Q

What is the half life of ADH and is it a stable molecule?

A

Unstable molecule with a half life of 10 minutes.

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133
Q

Where is V1 receptor found in and its function?

A

Found in smooth muscles where it causes vasoconstriction via InsP3/DAG calcium influx pathway.

134
Q

What are the functions of oxytocin?

A
  • Trigger of milk let-down reflex during breast feeding(milk ejection reflex)
  • Increases thirst because it is an agonist for V1 and V2 receptor.
135
Q

Other than the supraoptic/paraventricular nuclei where else does the AV3V neurones project towards and why?

A

Median pre-optic area of the hypothalamus which induces thirst when there is an increase in osmolality.

136
Q

What happens when we binge drink?

A

There is a decreased in osmolality, sensed by the AV3V receptors neurones project towards

i. Supraoptic and paraventricular nuclei - Suppress ADH hormone release.
ii. Median pre-optic region of hypothalamus - Suppress thirst

137
Q

What is the effect of osmolality on the circulating ADH?

A

Increased osmolality above 285mOsm results in a linear increase in ADH release.

138
Q

What response when there is maximal ADH?

A

Maximal absorption of water so concentrated urine produced with a volume about 300-400 ml/day and osmolality of 1400mOsm.

139
Q

What response when there is no ADH?

A

No absorption of water from AQP2. Very diluted urine of volume 25L/day and osmolality of 60-90mOsm produced.

140
Q

How does max osmolality differ in infants and what should be ensured in the infant formula?

A

Max osmolality that they can achieve is not 1400 but 500mOsm. Infant formula should not be too concentrated

141
Q

How do you calculate volume of water needed to clear a substance out based on osmolality of human?

A

Volume of water = Osmolality of substance/1400

142
Q

Going back to the infants case, what happens when their max osmolality is only 500 and formula given with an osmolality of 1000

A

Volume needed = 1000/500 = 2L which may result in excessive volume lost leading to hypovolaemia and dehydration. Leading to a lot of problems.

143
Q

What are the dominant osmolytes in the circulation?

A

Na+/Cl-

144
Q

Do circulating osmolytes dominate more than ingested osmolytes?

A

No. Ingested osmolytes such as protein and carbohydrate which enter circulation from gut in a water soluble form are more dominant because they are ingested in much larger quantities than sodium and chloride.

145
Q

What happens to carbohydrates post absorption? How does it differ in diabetes mellitus?

A
  • Converted into simple sugar so taken up by cells so not significantly contributing to osmolality.
  • In diabetes mellitus, there is a breakdown of carbohydrate into carbon dioxide which is eliminated and water so only a transient increase in osmolality.
146
Q

What happens to protein post absorption? What happens to nitrogen released?

A
  • Protein broken down into amino acids and rapidly taken up by cells so change is plasma osmolality is small.
  • Nitrogen can be removed through urea which has a high renal clearance so contribution to osmolality is of low significance.
147
Q

Which is cleared more rapidly Na+/K+?

A

Potassium so is has a lower contribution to osmolality.

148
Q

When does hyperosmolar hyperglycaemic state occur?

A

Occurs in diabetes mellitus where glucose concentration in plasma is really high that it contributes largely to plasma osmolality and can increase it up to 320mOsm when above 33mM.

149
Q

What physiological responses seen in hyperosmolar hyperglycaemia state?

A
  • Strong thirst drive
  • Cellular dehydration
  • If sufficient water intake to lower glucose concentration, hyponatraemia can occur.
150
Q

What are the effects of hyperosmolar hyperglycaemia state?

A
  • Confusion
  • Seizures
  • Increase in blood viscosity
151
Q

Does osmoregulation regulate concentration or volume?

A

Concentration regulated which will alter volume.

152
Q

What volume is regulated by the body and why?

A

The effective circulating volume. Total extracellular water content cannot be easily measured but extracellular water volume changes together with effective circulating volume.

153
Q

What does the juxtaglomerular apparatus consist of?

A
  1. Macula densa in the distal tubule

2. Granular cells (juxtaglomerular cells) in the afferent arteriole.

154
Q

Explain the Renin-Angiotensin-Aldosterone System (It is a negative feedback mechanism)

A
  1. When there is a fall in Na+ ions delivery to the distal tubule, it is detected by the macula densa.
  2. Signal trasmitted to the juxtaglomerular cells in the afferent arteriole which secretes renin as a result.
  3. Renin converts angiotensinogen from liver to Angiotensin 1.
  4. ACE enzyme converts Angiotensin 1 to Angiotensin 2.
  5. Angiotensin 2 has 3 significant functions:
    a) Efferent vasoconstriction - Increases GFR
    b) Increase sodium reabsorption at the proximal tubule.
    c) Stimulates aldosterone release from adrenal cortex.
    - Increases sodium reabsorption from the distal tubule and collecting duct.
  6. Increase in GFR and Sodium delivery
155
Q

What are the 2 main physiological triggers of aldosterone release?

A
  1. Angiotensin 2

2. Hyperkalaemia

156
Q

What are the 4 drug targets to inhibit renin-angiotensin system?

A
  1. ACE inhibitors - Ramipril, captopril
  2. AT1 receptors - ending with sartan Irbesartan, candesartan
  3. Aldosterone antagonist - Spironolactone (potassium sparing)
  4. Renin inhibition - Aliskiren
157
Q

What is the cellular mechanism of Angiotensin 2?

A
  1. Ang II binds to the AT1 receptor in the smooth muscle and granule cells.
  2. Activates Gq which results in InsP3 and DAG leading to increased intracellular calcium release.
  3. This can cause smooth muscle constriction.
158
Q

Why are AT1 antagonist preferred over ACE inhibitors?

A

Does not have the side effect of cough but more expensive.

159
Q

What are the 5 key actions of Angiotensin II to increase circulating volume?

A
  1. Vasoconstriction
  2. Increase Na/H exchange at proximal tubule so more sodium and water reabsorption occurs.
  3. Release aldosterone which increases sodium and water reabsorption at the distal tubule and collecting duct.
  4. Releases ADH which increases AQP2 synthesis and insertion which leads to increased water reabsorption at the collecting duct (medullary region)
  5. Induces thirst acting on medial pre-optic region of hypothalamus.
160
Q

What happens in a haemorrhage?

A

Decreased effective circulating volume -> Decreased arterial blood pressure –> Increased sympathetic activity on the granule cells which increase renin secretion. –> Fall in blood pressure also sensed by afferent arteriole causing a decrease in wall tension so renin released.

161
Q

What are the 3 effects of activating sympathetic innervation to the afferent arteriole?

A
  1. Vasoconstriction upstream to the granule cells which causes a further fall in pressure sensed by granule cells .
  2. Direct renin secretion from the granule cells.
  3. Afferent vasoconstriction causes decrease in flow so decreased hydrostatic pressure so GFR decreases.
162
Q

Where are the 2 areas to which noradrenaline binds to and what is the difference in their mechanisms?

A
  1. Smooth muscle a1 adrenoreceptors- Gq - Intracellular calcium release so vasoconstriction.
  2. Granule cells B1 adrenoreceptors - Gs - Renin release
163
Q

What are the 3 stimulus for renin release?

A
  1. Low afferent arteriole pressure releases renin
  2. Direct sympathetic stimulation
  3. Fall in venous pressure causes a fall in pressure in vasa recta which increase fluid uptake from renal interstitial space. This shows greater loss of fluid in nephron so less sodium delivery to the distal tubule.
164
Q

What is the acute response to haemorrhage due to increased ADH?

A

Hyponatraemia because sodium reabsorption is not increased whereas only water reabsorption is increased. This is acute response to haemorrhage.

165
Q

What effect does volume regulation have on osmoregulation?

A

It disturbs osmoregulation. If there is severe loss of volume, body will accept a lower osmolality to maintain low volume.

166
Q

What causes an ADH release

A
  • Increased osmolality
  • Nicotine
  • Stress
  • Hypovolaemia
167
Q

What suppresses ADH release?

A
  • Decreased osmolality
  • Fluid overload
  • Alcohol
168
Q

What stimulates the release of Atrial Natriuretic Peptide (ANP)

A

Increased venous return that increases atrial filling

169
Q

Where does the ANP go once it has been released?

A

Travels to the kidney to bind to ANP a/b receptors which activate guanylyl cyclase to increase cGMP.

170
Q

What is the name of the protein similar to ANP released by the kidney?

A

Urodilatin

171
Q

What are the 3 effects of ANP?

A
  • Inhibition to Na+/K+ ATPase pump which results in afferent vasodilation –> Increased GFR
  • Inhibit Na+/Cl- channel in distal tubule
  • Inhibit ENac in cortical collecting duct
    ALL OF THESE INHIBIT SODIUM REABSORPTION AND SO NATRIURIA.
172
Q

What are the functions of prostaglandin?

A

Increase sodium excretion

173
Q

If NSAID used, what could potentially happen for those with renal failure?

A

NSAIDS inhibit prostaglandins so sodium retention will occur.

174
Q

Where is dopamine synthesised?

A

In the kidneys mainly by the epithelial cells in the proximal tubule.

175
Q

Where does dopamine act on and what is its effect?

A

D1 receptors to increase cAMP which decrease Na/H exchanger activity at the proximal tubule.
Increased sodium excretion.

176
Q

What is the definition of pH?

A

pH = -Log 10 [H+]

177
Q

Equation of HCO3-

A

CO2 + H20 -> HCO3- + H+

178
Q

What are the normal values for arterial and venous

i. pH
ii. HCO3-
iii. PC02

A 
arterial
i. 7.4
ii. 24mM
iii. 40mmHg
Venous 
i. 7.35
ii. 25mM
iii. 46mmHg
179
Q

Henderson-Hasselbac equation

A 
pH = pK +log 10 [base/acid]
base = HCO3-
acid = H2CO3 = 0.03*PCO2
180
Q

What is the relationship between [H+], [C02] and [HC03-]

A

[H+] PROPORTIONAL TO [CO2]/[HCO3-]

181
Q

Where does the nett hydrogen ion production occurs through which processes

A
  1. ATP is hydrolysed
  2. Anaerobic through lactate production
  3. When ketones are produced during diabetes mellitus
  4. Ingestion of acids
182
Q

How is the bicarbonate absorbed in the proximal tubule?

A

Na/3HCO3 co-transporter

183
Q

Does Bicarbonate ion have a tubular maximum Tm limit??

A

Yes of 25mM anything more is excreted3

184
Q

What happens differently when the source of CO2 is not from the filtrate but the vasa recta?

A
  • Bicarbonate production

- Luminal H+ buffered by HPO4 (2-)

185
Q

How is H+ ions secreted in the distal tubule and where does it occur?

A
  • H+/K+ ATPase
  • H+ ATPase
    occurs in the a intercalated cells of distal tubule.
186
Q

What are the 2 mechanisms involved in the generation of HC03-?

A
  • HP04 (2-)
  • Ammonium release during the conversion of glutamate into glutamic acid and conversion of this into a ketoglutarate.
  • Ammonium dissociates into ammonia and hydrogen ion which at the apical membrane enters the filtrate.Increased carbon dioxide and water production through Carbonic anhydrase. Diffuse across brush border to generate more bicarbonate ions that are absorbed into interstitium.
187
Q

What happens to the pH along the nephron?

A

pH will fall due to reabsorption of bicarbonate ions which will make urine more acidic.

188
Q

What is the cause of respiratory acidosis?

A

Hypoventilation

189
Q

What occurs during respiratory acidosis?

A
  • Increase in carbon dioxide.
  • Curve shifts to increase hydrogen and bicarbonate ions.
  • Decrease in pH
190
Q

What is the correction and compensatory mechanism for respiratory acidosis?

A

Correction - Ventilation corrected

Compensatory - Metabolic compensation by increasing bicarbonate secretion and reabsorption

191
Q

What are the causes of respiratory alkalosis?

A
  • Hyperventilation due to altitude change, stress, CNS tumour.
192
Q

What occurs during respiratory alkalosis?

A
  • Decreased Carbon dioxide, shifts the curve to increase carbon dioxide, water and decrease hydrogen ions and bicarbonate ions.
  • pH increase
  • Decrease in bicarbonate ions.
193
Q

What is the correction and compensatory mechanisms for respiratory alkalosis?

A

Correction - Fix hyperventilation
Compensation - Metabolic by decreasing bicarbonate production and reabsorption, increasing bicarbonate excretion through filtrate via HC03- /Cl- antitransporter at the apical membrane of proximal tubule.

194
Q

What causes metabolic acidosis?

A

Diarrhoea, Ketoacidosis, Lactic acid build up, acid ingestion (aspirin poisoning)

195
Q

What occurs during metabolic acidosis?

A
  • Increase in hydrogen ions -> Decrease in pH

- Curve shifts to produce more carbon dioxide and water

196
Q

Correction and compensation mechanisms

A

Compensation - Hyperventilation to eliminate carbon dioxide. So pH can drop to normal levels
Correction - Increase bicarbonate production and reabsorption over time to decrease hydrogen ions available. Increase H+ ions excretion via Na/H+ antiport pump.

197
Q

What causes metabolic alkalosis?

A

Vomitting, Indigestion medications

198
Q

What occurs during metabolic alkalosis?

A
  • Decrease in hydrogen ions

- Curve shifts to increase hydrogen and bicarbonate ions.

199
Q

Correction and compensation mechanisms

A

Compensation - Respiratory via hypoventilation to increase Carbon dioxide levels that will Increase pH to normal levels.
Correction - Decreased secretion of hydrogen ion which will lead to decreased reabsorption and generation of bicarbonate ions so more bicarbonate ions excreted.

200
Q

How is the anion gap measure?

A

[Na+] - [Cl-] - [HCO3-]

201
Q

Why is there an anion gap in a normal person?

A
  • Exacerbated by divalent cations such as calcium and mg2+

- Partially by other anions such as HPO4(2-)

202
Q

What can lead to an increase in anion gap?

A

Increase shows an increase in anions

  • Lactate
  • Ketoacidosis
  • Acid ingestion from aspirin overdose
  • Accumulation of sulfate, urate and hippurate due to renal failure
203
Q

What causes hyperkalaemia?

A
  • End stage renal failure
  • Crush injuries
  • Blood transfusion
  • Cytotoxic drugs
  • Insulin deficiency
  • Over use of K+ sparing diuretics such as spironolactone
204
Q

What is the consequence of hyperkalaemia?

A

Cardiac dysrhythmias

205
Q

What are the treatments available for hyperkalaemia?

A
  • Potassium restricted diet
  • If due to insulin deficiency - Insulin given.
  • Glucose given
206
Q

What causes hypokalaemia?

A
  • Furosemide (NKCC inhibitor-loop diuretic)

- Insulin overdose

207
Q

Consequence of hypokalaemia

A

Cardiac dysrhythmias

208
Q

What treatments available for hypokalaemia?

A

Acute - IV K+

Chronic - Oral K+

209
Q

What are the sites of renal potassium exchange?

A

Proximal tubule - Reabsorption passively and paracellularly with water.
TAL - NKCC2 transporter but Potassium re-enters filtrate via ROMK
Distal tubule and collecting duct - ROMK (under Aldosterone control), Ca2+ activated potassium channel due to positive charge.

210
Q

How do most diuretics increase distal potassium secretions?

A
  • Increasing sodium delivery to distal tubule

- Increasing water in the filtrate to reduce potassium concentration

211
Q

How is calcium reabsorbed in the nephron?

A
  • TAL via positive charge created by potassium ions that enter filtrate through ROMK
  • Proximal tubule: Calcium moves transcellularly proportional to water movement
212
Q

How is sulfate reabsorbed in the proximal tubule?

A
  • NaS1 cotransporter

- 3Na+/1 SO4 (2-)

213
Q

Where is erythropoietin synthesised?

A

Peritubular fibroblasts in the renal cortex

214
Q

What stimulates the release of EPO?

A

Hypoxia

215
Q

What is the transcription factor that stimulates EPO enhancer?

A

HIF-2

216
Q

What happens to EPO in chronic renal failure? What is the exception to the rule?

A
  • Decreased EPO production

- Except in polycystic kidney disease

217
Q

What is the treatment for EPO deficiency in someone with renal failure?

A

EPO recombinant

218
Q

What is the risk of EPO abuse?

A
  • Increased red blood cell production
  • Increased haematocrit
  • Increased blood viscosity
  • Increased risk of thrombosis
219
Q

Why are patients with renal failure calcium deficient?

A
  • Kidney needed to convert 25-hydroxyvitaminD3 into 1,25-dihydroxyvitD3.
220
Q

Define what shock is

A

It is a state of inadequate perfusion.

221
Q

Shock can be due to 2 states and give and example of what might cause them

A
  1. Low CO - Hypovolaemia , cardiogenic shock
  2. High CO - Anaphylactic shock, sepsis which causes massive systemic vasodilation which will cause blood pressure to fall.
222
Q

What are the causes of cardiogenic shock?

A
  • Myocardial infarction
  • Aortic stenosis
  • Cardiac tamponade where there is a fluid build up in the pericardium and compresses the heart
223
Q

Explain the effects of cardiogenic shock.

A
  • Decrease in CO -> Decrease in Blood pressure -> Decrease in effective circulating volume
  • Increase in blood accumulation in the venous (capacitance vessels) so increase in central venous pressure.
  • Decrease in ABP sensed by baroreceptors which causes
    i. Increases peripheral vasoconstriction
    ii. Renin angiotensin system activation via direct stimulation, decreased afferent arteriole pressure and decreased delivery of sodium ions to distal tubule sensed by macula densa.
224
Q

What is the volume receptor reflex on the venous end?

A

Increased volume will result in increased blood pressure which will inhibit sympathetic activity to the kidney and suppress ADH release.

225
Q

How does the Bainbridge reflex work?

A

Increased venous return, Increased Central venous pressure, increased atrial filling, detected by stretch receptors which sends signal to the NTS - NA inhibit parasympathetic. RVLM increase sympathetic.

226
Q

What can cause a decreased in distension?

A
  • Gravity so standing
  • Haemorrhage
  • Dehydration
227
Q

What can cause an increase in distension?

A
  • Supine position
  • Fluid overload
  • Over transfusion
  • Cardiogenic ventricular failure
228
Q

Which reflex is faster baroreceptor or volume reflex?

A

Baroreceptor reflex. If their nerves cut accidentally during a surgery, initially blood pressure not very well controlled but volume reflex takes over over time and stabilises it.

229
Q

What happens during hypovolaemia?

A
  • Decreased effective circulating volume
  • Decreased ABP
  • Baroreceptor stimulated when detected by aortic arch and carotid sinus.
230
Q

What are the effects of baroreceptor effects?

A
  • Increased heart rate
  • Increased contractility
  • Increased venous return due to venoconstriction
  • Increased arteriolar constriction which increases total peripheral resistance and decreased capillary hydrostatic pressure so more reabsorption occurs.
  • Stimulates paraventricular and supraoptic nuclei to release ADH via posterior pituitary to increase water reabsorption
231
Q

What are the causes of hypovolaemia?

A
  • Haemorrhage
  • Dehydration
  • Burns
  • Diarrhoea/vomitting
232
Q

What are the renal consequences of shock?

A
  • Hypoxia
    i. Tissue damage - K+ overloading on kidneys
    ii. Anaerobic respiration - Metabolic acidosis
    iii. Acute renal failure
    iv. Vasoconstriction due to alpha 1 adrenoreceptors
233
Q

What are the adaptive responses to renal shock?

A
  • Renin angiotensin system activation
    i. Angiotensin II to cause afferent vasoconstriction to decrease GFR
    ii. Aldosterone to excrete potassium and increase sodium reabsorption in distal and collecting ducts.
  • ADH release
234
Q

What happens to sodium concentration in renal shock?

A

Hyponatraemia but it is transient and tolerant in order to increase effective circulating volume

235
Q

What are the treatments available for haemorrhage?

A
  • Colloid: Large molecular weight substance that remains intravascular. It could be albumin, gelatin, dextrins
  • Crystalloids: Substances like saline or sodium chloride where osmolality is maintained
236
Q

What is the pathways of flow of urine?

A
  • Minor calynx
  • Major calynx
  • Renal Pelvis
  • Ureter
  • Bladder
  • Urethra
237
Q

How does urine propagate via urethra?

A

Peristalsis of smooth muscles

238
Q

Where are the likely sites of obstruction of stones?

A
  • Uteropelvic junction
  • Pelvic brim
  • When it pierces through the bladder at an angle
239
Q

What are the treatments for kidney stones?

A
  • Percutaneous nephrostomy: Enters the renal pelvis to remove pressure
  • Extracorporeal shock wave lithotripsy
240
Q

What are the layers of the bladder wall?

A
  • Urothelium
  • Lamina propria
  • Detrusor
  • Serosa
241
Q

What are the special characteristics of the urothelium?

A
  • Tight junctions between cells to reduce permeability

- Umbrella cells to prevent destruction of epithelial layer from the acidic urine.

242
Q

What does the lamina propria contain?

A
  • Contains blood vessels, lympatics, nerves and interstitial cells of CAJAL.
  • Sensory nerve terminals which contain chemical and mechanoreceptors that sense filling state of bladder
  • Interstitial cells: Research ongoing that they mediate signalling between urothelium and detrusor.
243
Q

What is the detrusor muscle innervated by and how does it respond to each stimulus?

A
  • Parasympathetic via sacral nerves (S2-S4) : M3 receptor via ACh. Contraction of detrusor
  • Sympathetic via hypogastric nerve (T12-L2): B3 adrenoreceptor. Relaxation of bladder.
244
Q

What is the voiding reflex?

A

Pudendal nerve (S2-S4) innervates external urethral sphincter.

245
Q

What are the layers in urethra?

A
  • Lamina Propria
  • Longitudinal
  • Circular
  • Striated muscles
246
Q

What systems are active and inactive during continence?

A
  • Parasympathetic : Inactive- Bladder relaxation
  • Sympathetic: Active- Bladder relaxation
  • Somatic: Active- Constricted external urethral sphincter
247
Q

What systems are active and inactive during voiding?

A
  • Parasympathetic: Active bladder contraction
  • Sympathetic: Inactivated bladder contraction
  • Somatic: Inactive- EUS relaxed
248
Q

What are the 2 main types of incontinence and what causes them?

A
  • Stress incontinence: Vaginal childbirth, weakening of pelvic floor muscles.
  • Urge incontinence: Detrusor overactivity
249
Q

Why does UTI cause an increase in urinary frequency?

A

Chemical stimuli increases bladder activity

250
Q

What effects seen if there is a spinal cord injury above T12 level?

A
  • Afferent nerves cannot send signals to CNS about bladder filling
  • Loss of somatic control: Pudendal nerve so constantly relaxed external urethral sphincter
  • Spinal reflex functioning so when bladder wall stretches, detrusor muscle contracts to allow outflow of urine.
251
Q

Below T12 spinal injury effect on voiding?

A
  • Damage to parasympathetic nerves.
  • Unable to contract the detrusor
  • Bladder fills abnormally
  • Increased pressure in bladder will force urine flow ourwards
252
Q

What are the pharmacological managements of an overactive bladder?

A
  • Muscarinic antagonists oxybutynin
  • Botulinum toxin: Inhibit acetylcholine release so decrease force of contraction of detrusor muscle
  • B3 adrenoreceptor agonist
253
Q

What are the causes of urinary outflow obstruction?

A

Benign Prostatic Hyperplasia

254
Q

How can Benign Prostatic Hyperplasia be treated?

A
  • 5 alpha reductase inhibitor: Finasteride: Reduce hypertrophy
  • Alpha 1 adrenoreceptor antagonist: Terazosin/tamsulosn: Relaxation of smooth muscle of prostate
  • Transurethral resection of prostate via a catheter
255
Q

What is creatinine concentration influenced by?

A
  • Age
  • Ethnicity
  • Body mass
  • Gender
  • Diet
  • Exercise
256
Q

What is the problem associated with using creatinine levels as an indicator of kidney disease?

A
  • Not sensitive to small changes

- Renal function needs to fall a lot for there to be a change in creatinine levels.

257
Q

What are the correction factors in regards to eGFR?

A
  • Age
  • Gender
  • Ethnicity
  • Creatinine
258
Q

Which is a more accurate method to measure kidney function eGFR or creatinine levels?

A

eGFR

259
Q

How can one define Chronic Kidney Disease

A
  • Irreversible

- Progressive condition of kidney degeneration

260
Q

How many stages can CKD be divided into and what characteristic of eGFR does each stage need to have?

A 
Stage 1: Normal GFR >90
Stage 2 : GFR 60-89
Stage 3: GFR 30-59
Stage 4 : GFR 15-29
Stage 5 : GFR <15
261
Q

What methods of treatment used in stage 5 CKD?

A
  • Dialysis either peritoneal or haemodialysis

- Transplantation

262
Q

What are the 6 causes of CKD?

A
  1. Systemic diseases - Diabetes, hypertension
  2. Immune mediated - Nephropathy either membranous or IgA
  3. Genetic - Polycystic kidneys
  4. Infectious disease - HIV, HBV, TB
  5. Arterial disease- Atherosclerosis
  6. Obstruction - tumours, stones, fibrosis
263
Q

What is the pathology seen on the kidney due to CKD?

A
  • Atrophied tubules

- Sclerosed glomeruli

264
Q

What is pathological changes in the kidney due to diabetic nephropathy?

A
  • Thickening of basement membrane
  • Glomerulosclerosis
  • Mesangial expansion due to increased matrix production stimulated by hyperglycaemia
265
Q

What functions of kidney affected from CKD?

A
  • Excretory functions
    1. Water
    2. Electrolytes
    3. Metabolites
    4. Acid.
    5. Drugs
  • Secretory functions
    1. EPO
    2. Vitamin D
266
Q

What happens to fluid in CKD?

A
  • Inability to excrete water load: Oedema, hyponatraemia, hypertension
  • Inability to concentrate urine (early) : Loss of diurnal rhythm, Diuresis
267
Q

What is the treatment for fluid overload for CKD?

A
  • Furosemide: Loop diuretic
  • Fluid restriction
  • Low salt diet
268
Q

What happens to electrolytes in CKD?

A
  1. Sodium - Loss of nephron so inability to excrete water and sodium. Causes hypertension and fluid overload. Ig sodium concentration not within normal ranges, it can cause seizures, confusion or coma.
  2. Potassium - Inability to excrete: Hyperkalaemia leading to cardiac arrythmias
  3. Bicarbonate ions: failure to excrete acid, equilibrium shift to increase CO2 to be removed by lungs resulting in metabolic acidosis.
269
Q

What changes can you see in an ECG due to hyperkalaemia?

A
  • T wave amplitude increased
  • Long PR interval
  • Long QRS complex
270
Q

What treatment used to prevent hyperkalaemia and hypernatraemia?

A
  • Salt restriction

- Potassium restriction diet

271
Q

What are the signs seen in metabolic acidosis?

A
  • Increased respiratory drive
  • Chest pain
  • Confusion
  • Bone pain
  • Dimineralisation of bone to act as buffer
272
Q

What treatment given for metabolic acidosis?

A

Sodium bicarbonate if not dialysis

273
Q

What hormones are produced by the kidney?

A
  • Hydroxylation of vitamin D3
  • EPO
  • Renin
274
Q

What effect seen when vitamin D3 cannot be hydroxylated in the kidney?

A
  • Hyperparathyroidism
  • Ectopic calcification due to bone resorption as calcium levels cannot be buffered by increase in calcium absorption from the gut
275
Q

What treatments prevent bone disease and ectopic calcification in CKD?

A
  • 1,25-dihydroxyvitamin D3 analogue
  • Phosphate binders
  • Calcimimetics which inhibit PTH secretion
  • Parathyroidectomy if nothing else works
276
Q

What is the effect of inability to produce EPO due to CKD?

A
  • Reduced exercise capacity
  • Impaired cognition
  • Increased risk of left ventricular hypertrophy
  • Increased risk of cardiovascular disease
277
Q

What is the treatment for renal anaemia?

A

EPO recombinant

278
Q

What is the treatment for hypertension in those with CKD?

A
  • Salt restriction
  • Diuretics
  • RAAS blockade (Sartan’s)
  • Anti-hypertensive meds
279
Q

What occurs when kidney fails to excrete substances due to CKD? URAEMIA

A

Accumulation of toxic waste products

  • Urea
  • Phosphate
  • Nitrogenous waste
  • Increase in creatinine after significant renal damage
280
Q

What is the treatment for uraemia in CKD?

A
  • Dialysis/transplantation
281
Q

Why one cannot treat uraemia with protein restriction?

A

Malnutrition will occur

282
Q

What happens to the kidney’s ability to excrete drugs?

A
  • Unable to excrete or metabolise certain drugs

- Increased risk of toxicity

283
Q

What is the treatment for drug toxicity in CKD?

A

Dosage adjustments

284
Q

How fast does Acute Kidney Injury (AKI) occur?

A

Hours to days, its a rapid decline in kidney function

285
Q

What are the stages in AKI? How do they differ in terms of creatinine levels and urine output?

A 
Stage 1
- Creatinine: 50-100% from baseline
- Urine output: <0.5ml/kg/hour for 6 hours
Stage 2
- Creatinine: 100-200% increase
- Volume <0.5/ml/kg/hr for 12 hours
Stage 3
- Creatinine: >200% increase
- Output <0.3 for 24 hours for anuria for 12 hours
286
Q

How are the causes of AKI categorised and explain how that could happen?

A
  1. Pre-renal
    - Perfusion failure
  2. Renal
    - Intrinsic disease of kidney
  3. Post-renal
    - Obstruction
287
Q

What can cause perfusion failure in AKI?

A
  • Hypotension
  • Hypovolaemia
  • Renal artery occlusion
288
Q

What can cause perfusion failure to be worse in AKI?

A

If patients are on drugs such as ACE Inhibitor- Ramipril as unable to increase blood pressure
AT1 antagonist- Sartans
NSAIDs
Diuretics (Spironolactone)

289
Q

How does the pathology of kidney differ in AKI?

A

Acute tubular necrosis

290
Q

What is the treatment for perfusion failure (pre-renal cause of AKI)

A
  • Fluid replacement
  • Stop drugs that interfere with blood pressure physiology (Renin inhibitor, ACE inhibitor, AT1 antagonist, diuretics)
  • Blood pressure support: Inotropic drugs - adrenaline, noradrenaline
  • Restore patency of artery due to occlusion by unblocking it
291
Q

What are the causes of post-renal AKI?

A

Obstruction due to

  • Stones
  • Tumour
  • Fibrosis
  • Benign prostate
292
Q

What is the treatment for obstruction?

A

Bypass or removal of obstruction via

  • Shock wave lithotripsy
  • Percutaneous nephrostomy
  • Bladder catheter
  • Tumour removal
  • Dilate strictures
293
Q

What are the renal causes of AKI?

A
  • Systemic disease: Vasculitis, SLE, Myeloma
  • Infection: HIV, endocarditis
  • Allergic: Acute interstitial nephritis
  • Drug toxicity: Gentamycin, NSAID, chemotherapy
  • Glomerulonephritis
294
Q

How does vasculitis result in kidney damage and AKI?

A
  • Anti-neutrophil cytoplasm antibodies (ANCA) produced
  • They activate neutrophils who then attach themselves to the endothelium
  • Phagocytose the endothelium until it becomes necrotic and inflammation occurs.
295
Q

How is inflammatory renal disease treated?

A
  • Steroids
  • Cyclophosphamide: chemotherapy drug
  • Plasma exchange
  • Azathioprine: Suppress immune system
296
Q

What are the 2 types of renal replacement therapy?

A
  • Dialysis: Peritoneal, haemodialysis

- Transplantation

297
Q

What is the difference between dialysis and transplantation in terms replacing kidney function?

A

Dialysis replaces water, electrolyte, acid, metabolite and drugs excretion but cannot produce erythropoietin, renin and vit D3 converting enzyme. Transplantation allows full function of kidney to be regained.

298
Q

How is blood filtered through dialysis?

A
  • Semi-permeable membrane separates patient’s blood with dialysis fluid.
  • Filtration occurs via diffusion (pressure gradient, distance), osmosis
  • Can alter dialysis fluid in order to accommodate to a particular need. EG too much water/alcohol consumed, osmolality of dialysis fluid increased so water leaves the patient’s blood and enters the dialysis fluid.
299
Q

What are the advantages of peritoneal dialysis?

A
  • Performed at home
  • Can do it 4x a day according to one’s own comfort
  • Can also do a continuous dialysis overnight.
300
Q

What are the disadvantages of peritoneal dialysis?

A
  • Risk of infection from catheter

- Risk of peritonitis

301
Q

Briefly describe haemodialysis

A
  • Performed at the hospital around 3 times a week and 4 hours per session.
  • Either have an AV fistula or central venous catheter which allows blood to flow out, passes through dialysis machine, dialysate and then blood enters back in.
302
Q

Can a patient with previous major abdominal operation be allowed to use peritoneal dialysis?

A

NO

303
Q

What are the problems associated with dialysis?

A
  • Anaemia
  • Increased risk of cardiac disease
  • Ectopic calcification ex arteries
  • Bone disease
  • Infection
304
Q

What are the advantages of transplantation?

A
  • Replaces all kidney function
  • Improved life expectancy
  • Improved quality of life
305
Q

Where is the new kidney placed?

A

Placed in the iliac fossa outside the peritoneum and old kidney left in place.

306
Q

What vessels supply the new kidney?

A

Iliac vessels

307
Q

Where can one get kidneys from?

A
  1. Live either from family or organ donors

2. Dead/cadaveric

308
Q

What need to match in a kidney transplantation?

A
  • Blood group
  • HLA types
  • Anti-donor antibodies (Cross match - serum of patient and donor mixed and complement added to see if there is a reaction. If no reaction then it is a good sign)
309
Q

What happens if there is a positive cross match?

A
  • Pre-formed antibodies stick to antigen activate complement and result in lysis and necrosis of kidney.
310
Q

Which filtrate concentration decreases significantly down the proximal tubule?

A
  • glucose
  • amino acids
  • bicarbonate
311
Q

What are the 3 ways in which urine sample can be analysed?

A
  • Appearance
  • Biochemistry
  • Microscopy
312
Q

What are the advantages of urinalysis?

A
  • Can be done easily at the GP practive
  • Non-invasive
  • Normal composition mostly known
  • Can be used for prerenal and renal diseases.
313
Q

What should the general appearance of urine look like?

A
  • Pale yellow and clear

- Concentrated urine darker in colour due to hydration

314
Q

What does the colour of these urine samples indicate?

  • Red
  • Red/Brown
  • Black
A

Red: Blood either from urethra, bladder or prostate
Red/brown: Conjugated bilirubin
Black: Melanin due to disseminated melanoma

315
Q

What can you identify in a urine from a microscopic examination?

A
  • Bacteria: Dipstick tests for nitrite production then culture and quantitate
  • Cells: Red and white cells
  • Casts: Hyaline can be noticed post exercise but if red cell cast shows kidney damage(Glomerulonephritis)
  • Crystals
316
Q

What factors can increase creatinine levels?

A

High meat intake diet

317
Q

What factors show a decreased excretion of creatinine?

A
  • Wasting disease
  • Malnutrition
  • Poor renal blood flow or function
318
Q

What factors cause an increase in urea secretion?

A
  • Excess protein in diet

- Increased protein catabolism due to malnutrition, uncontrolled type 1 diabetes, infections, burns

319
Q

What factors cause a decrease in urea secretion?

A
  • Low protein diet
  • Glomerular nephritis
  • Poor renal blood supply
320
Q

What is the effect of a decreased urea secretion?

A
  • Hyerammonaemia and ammonium crosses BBB

- This can lead to lethargy, irritability and finally coma

321
Q

What can cause an increased glucose presence in urine?

A
  • Metabolic hyperglycaemia seen in diabetes mellitus type 1, anxiety, phaeochromocytoma
  • Reduced renal threshold during pregnancy
  • Tubular malfunction
322
Q

What is phaeomachromocytoma?

A
  • Tumour of the adrenal glands
323
Q

How does phaemachromocytoma cause hyperglycaemia?

A

Increased adrenaline production that causes increased conversion of glycogen into glucose.

324
Q

How do you treat phaeomachromocytoma?

A
  • Adrenal gland tumour removal surgey

- Blockers such as phenoxybenzamine or propanolol

325
Q

What is PKU -phenylketouria?

A
  • Phe hydroxylase deficiency so accumulation of hydrophobic Phe that can enter blood brain barrier
326
Q

What causes PKU?

A
  • It is a genetic condition due to deficiency of Phe hydroxylase.
327
Q

What are the symptoms of PKU?

A
  • Early: Fits, irritability

- Later: Mental retardation

328
Q

What causes proteinuria pre-renally?

A
  • High concentration in plasma of those of low molecular weight
329
Q

What causes proteinuria renally?

A
  1. Glomerular destruction which leads to increased permeability.
  2. Tubular: Impaired reabsorption
  3. Secreted: Secretion by kidney or epithelium of urinary tract.
330
Q

What is the percentage of body fluid distribution in these compartments?

  • Plasma
  • Interstitial
  • Transcellular
  • Intracellular
A

Plasma: 5%
Interstitial: 16%
Transcellular: 2 %
Intracellular 35%

331
Q

How is the distribution of microvilli throughout the nephron?

A

Proximal convoluted tubule with highest density of microvilli but density decreases down the nephron and by the time it reaches distal convoluted tubule, there is no more microvilli.

Foundations 3 (8 decks)

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