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Semester 4: Nutrition and Metabolism > PBL Topic 4 Case 7 > Flashcards

PBL Topic 4 Case 7 Flashcards

1
Q

Identify 7 functions of the kidneys

A
  • Excretion of waste products
  • Water + Electrolyte balance
  • Regulation of body fluid osmolality
  • Regulation of arterial pressure
  • Regulation of acid-base balance
  • Secretion, metabolism and excretion of hormones
  • Gluconeogenesis
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2
Q

Identify four waste products that are excreted by the kidneys

A
  • Urea (from amino acid metabolism)
  • Creatinine (from muscle creatine)
  • Uric acid (nucleic acids)
  • Bilirubin (from haemoglobin breakdown)
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3
Q

Why must water and electrolyte excretion precisely match intake?

A
  • If intake exceeds excretion, the amount of substance in the body will increase
  • If intake is less than excretion, the amount of substance in the body will decrease
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4
Q

Briefly identify 2 ways that the kidneys regulate arterial pressure

A
  • By excreting variable amounts of sodium and water

- By secreting vasoactive factors, e.g. renin, that lead to formation of vasoactive products, e.g. angiotensin II

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5
Q

Briefly describe how the kidneys regulate erythrocyte production

A
  • Fibroblasts secrete erythropoietin
  • Especially during hypoxia
  • Which stimulates the production of red blood cells
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6
Q

Briefly outline how the kidneys regulate vitamin D.

A
  • Hydroxylate vitamin D to calcitriol
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7
Q

Identify 3 roles of vitamin D

A
  • Calcium deposition in bone
  • Calcium reabsorption in GI tract
  • Calcium and phosphate regulation
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8
Q

Outline the kidneys role in gluconeogenesis

A
  • Synthesise glucose from amino acids
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9
Q

Outline the physiological anatomy of the kidneys

A
  • Surrounded by fibrous capsule
  • Contains outer cortex and inner medulla
  • Medulla is divided into pyramids by cortex columns
  • Base of each pyramid terminates in the papilla
  • Papilla projects into renal pelvis
  • Urine from papilla is collected by minor calyces which is collected by major calyces
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10
Q

Outline the arterial supply of the kidneys

A
  • Renal artery enters hilum and gives off lobar arteries
  • Which give off interlobar arteries
  • Which give off arcuate arteries
  • Which give off interlobular arteries
  • Which give off afferent arterioles
  • Which lead to glomerular capillaries
  • Distal end of glomerular capillaries forms efferent arterioles
  • Which lead to peritubular capillaries
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11
Q

How does hydrostatic pressure differ in the glomerular and peritubular capillaries

A
  • High hydrostatic pressure in glomerular capillaries, causing rapid filtration
  • Low hydrostatic pressure in peritubular capillaries, causing fluid reabsorption
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12
Q

Outline the venous drainage of the kidneys

A
  • Peritubular capillaries drain into interlobular veins
  • Which drain into arcuate veins
  • Which drain into interlobar veins
  • Which drain into the renal vein which leaves the kidney through the hilum
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13
Q

Identify the two main parts of a nephron

A
  • Glomerulus, through which large amounts of fluid are filtered from the blood
  • Tubule, where the filtered fluid is converted into urine
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14
Q

How many nephrons are there in each kidney? Can the kidney regenerate new nephrons?

A
  • 1 million nephrons

- No

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15
Q

Describe the hydrostatic pressure in the glomerular capillaries

A
  • High (60 mm Hg)
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16
Q

What happens to fluid that is filtered from the glomerular capillaries?

A
  • Flows into Bowman’s capsule which encases the glomerular capillaries
  • Fluid then flows into PCT
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17
Q

Is the PCT in the cortex or medulla of the kidney?

A
  • Cortex
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18
Q

What happens to fluid after it passes through the proximal tubule?

A
  • Flows into the loop of Henle

- Which is formed from a descending and ascending loop

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19
Q

How does thickness change in the loop of Henle?

A
  • Walls of descending limb and lower ascending limb are thin

- The ascending limb thickens as it enters the cortex

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20
Q

Is the loop of Henle located in the cortex or medulla of the kidney?

A
  • Both
  • Dips from cortex to medulla
  • Ascending limb thickens as it enters the cortex
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21
Q

What happens to fluid after it passes through the ascending limb of the loop of Henle?

A
  • Enters the DCT
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22
Q

Does the DCT lie in the cortex or medulla?

A
  • Cortex
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23
Q

What happens to fluid after it passes through the DCT?

A
  • Flows into connecting tubules
  • Which flows into cortical collecting tubules
  • Which leads to cortical collecting duct
  • Which runs downward and becomes the medullary collecting duct
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24
Q

What happens to fluid after it passes through the collecting ducts?

A
  • Passes into the renal pelvis through the tips of the renal papillae
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25
Q

Identify two types of nephrons and how they differ from one another in their structure

A
  • Cortical nephrons, located in outer cortex, short loop of Henle
  • Juxtamedullary nephrons, located in medulla, long loop of Henle
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26
Q

How do the two types of nephrons differ from one another in their vascular supply

A
  • Cortical nephrons, surrounded by peritubular capillaries

- Juxtamedullary nephrons, surrounded by vasa recta that loop downward like the loop of Henle

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27
Q

Express urinary excretion rate mathematically

A
  • Filtration rate - reabsorption rate + secretion rate
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28
Q

Identify a substance that is not filtered from the glomerular capillaries into Bowman’s capsule

A
  • Protein

- Since the glomerular capillaries are impermeable to protein

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29
Q

Identify 4 substances that are reabsorbed in the tubules

A
  • Water
  • Electrolytes
  • Amino acids
  • Glucose
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30
Q

Why are calcium and fatty acids sometimes not freely filtered in the glomerulus?

A
  • They may be bound to plasma proteins
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31
Q

Identify two factors that determine glomerular filtration rate

A
  • Balance of hydrostatic and colloid osmotic forces

- Capillary filtration coefficient (Kf)

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32
Q

Identify two factors that determine the capillary filtration coefficient

A
  • Permeability

- Surface area

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33
Q

Identify two reasons that the glomerular capillaries have a much higher rate of filtration that most other capillaries

A
  • High hydrostatic pressure

- High Kf

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34
Q

What is the average GFR in ml/min

A
  • 125 ml/min
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35
Q

What is filtration fraction and what is its value in the kidneys?

A
  • The fraction of plasma flow that is filtered

- 20% (of plasma flowing through kidney is filtered through glomerular capillaries)

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36
Q

How is filtration fraction calculated mathematically

A
  • GFR / Renal Plasma Flow
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37
Q

Identify the structure of the glomerular capillary membrane and the features of each which increase filtration

A
  • Endothelium (with fenestrations)
  • Basement membrane (with proteoglycan fibrillae)
  • Epithelial cells (podocytes) (with slit pores)
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38
Q

What is the importance of the negative charges in the endothelium, basement membrane and epithelial cells

A
  • Hinders passage of plasma proteins
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39
Q

Identify two forces that promote filtration

A
  • Hydrostatic pressure in glomerular capillaries, (glomerular hydrostatic pressure)
  • Colloid osmotic pressure of the proteins in Bowman’s capsule
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40
Q

Identify two forces that opposes filtration

A
  • Hydrostatic pressure in Bowman’s capsule outside the capillaries
  • Colloid osmotic pressure of the glomerular capillary plasma proteins
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41
Q

Why does the plasma protein concentration increase from the afferent to efferent arterioles?

A
  • 20% of fluid is filtered into Bowman’s capsule

- Concentrating the glomerular plasma proteins that are not filtered

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42
Q

Identify two factors that influence glomerular capillary colloid osmotic pressure

A
  • Arterial plasma colloid osmotic pressure

- Filtration fraction

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43
Q

Identify two factors that would increase filtration fraction

A
  • Increasing GFR

- Reducing renal plasma flow

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44
Q

Identify three factors that affect glomerular hydrostatic pressure

A
  • Arterial pressure
  • Afferent arteriolar resistance
  • Efferent arteriolar resistance
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45
Q

Outline the biphasic effect of efferent arteriolar resistance on GFR

A
  • Moderate constriction of efferent arterioles increase resistance to outflow
  • Which raises GFR
  • Severe constriction increases colloid pressure
  • Which decreases GFR
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46
Q

How is renal blood flow determined?

A
  • Difference between renal artery and vein hydrostatic pressure
  • Divided by renal vascular resistance
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47
Q

Where does most renal vascular resistance take place? How is this resistance controlled?

A
  • Interlobular arteries
  • Afferent arterioles
  • Efferent arterioles
  • Sympathetic nervous system
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48
Q

What is autoregulation?

A
  • Mechanism by which renal blood flow and GFR remains relatively constant
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49
Q

Outline the renal blood flow to the medulla

A
  • Blood flow to medulla accounts for 1% of blood flow

- Supplied by vasa recta from peritubular capillary system

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50
Q

Identify hormones that constrict arterioles and reduces GFR

A
  • Noradrenaline
  • Adrenaline
  • Endothelin
  • Angiotensin II
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51
Q

Identify an autacoid that decreases vascular resistance and increases GFR

A
  • Nitric oxide
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52
Q

Identify autacoids and hormones that cause vasodilation and increases GFR

A
  • Prostaglandins E2 and I2

- Bradykinin

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53
Q

What is glomerulotubular balance?

A
  • Adaptive mechanisms in renal tubules

- That allow them to increase their reabsorption rate when GFR rises

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54
Q

Where are macula densa cells located and what is their role?

A
  • DCT

- Sense changes in volume delivery to the distal tubule

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55
Q

Outline the effect of a reduced GFR on macula densa cells

A
  • Reduced GFR slows the flow rate in the loop of Henle
  • Causing increased reabsorption of NaCl in the ascending loop of Henle
  • Reducing concentration of NaCl at macula densa cells
  • Decreasing resistance to blood flow (increasing GFR)
  • And increasing release of renin from juxtaglomerular cells (increasing GFR)
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56
Q

Identify the role of renin in raising GFR

A
  • Increases formation of angiotensin I
  • Which is converted to angiotensin II
  • Which constricts efferent arterioles
  • Increasing hydrostatic pressure and returning GFR to normal
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57
Q

Outline the purpose myogenic mechanism of renal blood flow

A
  • Ability of blood vessels to resist stretching during increased arterial pressure
  • To maintain a constant renal blood flow and GFR
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58
Q

Outline the role of calcium ions in the myogenic mechanism of renal blood flow

A
  • Stretch of vascular walls increases movement of calcium ions into cells from extracellular fluid
  • Which causes them to contract
  • Which prevents over-distension of the vessel
  • And increases vascular resistance
  • Which helps prevent excessive increases in renal blood flow and GFR
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59
Q

Why does a high protein intake increase renal blood flow / GFR?

A
  • Increased release of amino acids into blood
  • Which are reabsorbed in proximal tubule
  • Which causes reabsorption of sodium in proximal tubule
  • Decreased sodium to macula densa
  • Which causes a decrease in resistance of the afferent arterioles
  • Which raises renal blood flow and GFR
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60
Q

Why does a high glucose intake increase renal blood flow / GFR?

A
  • Glucose causes reabsorption of sodium
  • Reduced delivery of sodium to macula densa
  • Activating tubuloglomerular feedback-mediate dilation of afferent arterioles
  • With increase in renal blood flow and GFR
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61
Q

Describe the tubular absorption of:

[A] Glucose and amino acids

[B] Ions in plasma

[C] Waste products

A
  • [A] Completely reabsorbed
  • [B] Variable absorption
  • [C] Poorly reabsorbed
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62
Q

Identify two ways in which water and solutes can be reabsorbed

A
  • Transcellular route through the cell membrane

- Paracellular route, through the tight junctions

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63
Q

What is ultra-filtration?

A
  • Reabsorption from interstitial fluid into peritubular capillaries
  • Passive process
  • Driven by hydrostatic and colloid osmotic pressure gradients
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64
Q

What is primary active transport?

A
  • Movement of solutes against an electrochemical gradient

- Requiring energy from hydrolysis of ATP by ATPase

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65
Q

Give an example of the primary activate transport ysstem

A
  • Reabsorption of sodium ions
  • Hydrolysis of ATP moves sodium out of cell
  • At same time potassium is transported to inside of cell
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66
Q

Identify two provisions for moving large amounts of sodium into the cell

A
  • Brush border increases surface area

- Sodium carrier proteins for facilitated diffusion

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67
Q

Identify two mechanisms of secondary active reabsorption

A
  • Co transport, interaction with carrier protein and transport together (e.g. sodium and glucose)
  • Counter-transport, diffusion of sodium into cell liberates energy to secrete hydrogen ions into tubule
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68
Q

Identify a substance that is reabsorbed by pinocytosis. Outline the process of pinocytosis

A
  • Protein
  • Attaches to brush border of luminal membrane
  • This portion invaginates to interior of cell and pinched off to form a vesicle
  • Once in cell, protein is digested into amino acids
  • Which are reabsorbed through basolateral membrane
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69
Q

What is meant by transport maximum? Identify an example of this

A
  • Limit to rate at which solute can be actively transported
  • Due to saturation of carrier proteins when amount of solute exceeds capacity
  • Glucose transport system in uncontrolled diabetes
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70
Q

What is gradient time transport

A
  • Limit to rate at which solute can be passively reabsorbed

- Increased by high diffusion gradient, high permeability increased time that the substance remains in the tubule

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71
Q

How does reabsorption of water occur and how does it change throughout the nephron

A
  • Active transport of solutes decreases their concentration
  • Which increases osmosis of water
  • Reduces throughout nephron as tight junctions become tighter
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72
Q

What is solvent drag?

A
  • As water is reabsorbed

- It carries solvents with it

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73
Q

Outline the process of chloride reabsorption

A
  • Sodium reabsorption causes transport of chloride ions due to electrical potentials
  • Water reabsorption increases chloride ion concentration which creates a concentration gradient
  • Chloride ions can be co-transported with sodium ions
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74
Q

Identify three features of the PCT that allow for reabsorption

A
  • Highly metabolic, lots of mitochondria for active transport
  • Apical brush border
  • Carrier proteins
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75
Q

Explain how bicarbonate ions are removed from the PCT

A
  • Secretion of H+ (by counter transport)
  • Which combines with bicarbonate ions
  • To form carbonic acid
  • Which dissociates into water and carbon dioxide
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76
Q

Outline substances that are secreted by the PCT

A
  • Bile salts
  • Oxalate
  • Urate
  • Catecholamines
  • Harmful drugs and toxins
  • PAH
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77
Q

What is the function of the descending part of the loop of Henle?

A
  • Simple diffusion of water

- Ascending part is impermeable to water

78
Q

Which section of the ascending part of the loop of Henle is adapted for reabsorption?

A
  • Thick segment
  • ATPase
  • Due to high metabolic activity and surface area
79
Q

Which part of the loop of Henle reabsorbs calcium, bicarbonate and magensium?

A
  • Thick ascending part
80
Q

Outline the process of sodium reabsorption in the thick ascending part of the loop of Henle

A
  • ATPase provides energy
  • To move sodium through the Na-K-Cl co-transporter across the luminal membrane
  • This releases energy which moves chloride and potassium ions into the cell against a concentration gradient
  • In a ratio of (1Na:1K:2Cl)
81
Q

Why is the distal tubule referred to as the diluting segment?

A
  • Reabsorption of ions via the Na-K-Cl transporter

- Impermeable to water and urea

82
Q

Identify the two cell types in the late distal tubule and cortical collecting tubule

A
  • Principal cells: Sodium and water reabsorption, potassium secretion
  • Intercalated cells: Potassium reabsorption and hydrogen secretion
83
Q

Describe the process of potassium secretion by principal cells

A
  • Potassium enters cell through sodium potassium ATPase pump

- Diffuses across luminal membrane into tubular fluid down concentration gradient

84
Q

Describe the process of hydrogen ion secretion by intercalated cells

A
  • Carbonic anhydrase catalyses reaction of H2O and CO2
  • To form carbonic acid
  • Which dissociated into hydrogen and bicarbonate ions
  • Hydrogen ions secreted into lumen by hydrogen-ATPase transport mechanism
85
Q

Outline the special characteristics of the medullary collecting duct

A
  • Its permeability is controlled by ADH
  • It is permeable to urea
  • Secretes protons against a large concentration gradient
86
Q

What is glomerulotubular balance?

A
  • Rate of reabsorption changes in response to tubular inflow

- To help prevent overloading of the distal tubular segments

87
Q

How is reabsorption calculated?

A
  • Kf x Net Reabsorptive Force
88
Q

Identify the four osmotic forces that represent the net reabsorptive force

A
  • Hydrostatic pressure in peritubular capillaires
  • Hydrostatic pressure in renal interstitium
  • Colloid pressure in peritubular capillary
  • Colloid pressure in renal interstitium
89
Q

Identify factors that increase the peritubular capillary hydrostatic pressure and the effect on reabsorption

A
  • Increased arterial pressure
  • Increase in resistance of afferent and efferent arterioles
  • Both of which decrease reabsorption
90
Q

Identify factors that influence the peritubular capillary colloid pressure

A
  • Increase in plasma protein concentration
  • Increase in filtration fraction
  • Both of which increase reabsorption
91
Q

What is meant by pressure natriuresis and diuresis?

A
  • Increase in arterial pressure

- Causes marked increase in urinary excretion of sodium and water

92
Q

Where is aldosterone secreted from?

A
  • Zone glomerulosa

- Of adrenal cortex

93
Q

What is the primary site of aldosterone action?

A
  • Principal cells

- Cortical collecting tubule

94
Q

What is the action of aldosterone?

A
  • Increased sodium reabsorption
  • Increased potassium secretion
  • By stimulating sodium-potassium ATPase pump on basolateral side of cortical collecting tubule
95
Q

Outline two clinical conditions in which aldosterone is affected?

A
  • Addison’s disease: absence of aldosterone so marked natriuresis and accumulation of potassium
  • Conn’s syndrome: excess aldosterone so sodium retention and potassium depletion
96
Q

When is angiotensin II secreted?

A
  • Low blood pressure or extracellular fluid volume
97
Q

What is the general action of angiotensin II?

A
  • Helps to increase blood pressure

- By increasing sodium and water reabsorption from renal tubules

98
Q

Identify three effects of angiotensin II secretion

A
  • Stimulates aldosterone secretion,
  • Constricting efferent arterioles
  • Stimulates sodium-potassium ATPase pump
99
Q

What is the general action of ADH?

A
  • Increases water permeability of distal tubule, collecting tubule and collecting duct epithelia
  • Causing reabsorption of water
  • To conserve water e.g. dehydration
100
Q

Outline the cellular action of ADH

A
  • Binds to V2 receptors in distal tubules, collecting tubules and duct
  • Which increases cAMP formation and PKA
  • Which stimulates movement of aquaporin-2 to luminal side of cell membrane
  • Which fuse with the cell membrane by exocytosis
  • To form water channels that permit rapid diffusion of water through the cells
101
Q

When is atrial natriuretic peptide released and what is its action?

A
  • Distension of atria
  • Reduces reabsorption of sodium and water in collecting ducts
  • Which increases urinary excretion
  • Helping to return blood volume back to normal
102
Q

Outline the principal action of PTH in the kidneys

A
  • Increases calcium reabsorption in DCT

- Decreases phosphate and magnesium reabsorption in loop of Henle

103
Q

Outline three effects of the sympathetic nervous system on reabsorption

A
  • Constricts renal arterioles, reducing GFR
  • Increased reabsorption in proximal tubule
  • Increased renin release and angiotensin II formation
104
Q

Outline the renal mechanism for excreting a dilute urine

A
  • Dilution in ascending limb of loop of Henle
  • Due to reabsorption of ions (impermeable to water)
  • Absence of ADH so reduces reabsorption in collecting ducts
105
Q

Outline the two basic requirements for forming a concentrated urine

A
  • High level of ADH in collecting ducts (to increase permeability for water absorption)
  • High osmolarity of renal medullary interstitial fluid (providing an osmotic gradient)
106
Q

What is the importance of urea recycling?

A
  • Absorption of urea into medullary interstitium from collecting ducts
  • Increases osmolarity in renal medulla
  • To increase reabsorption of water to produce concentrated urine
107
Q

Outline the countercurrent mechanism

A
  • Blood enters and leaves medulla through vasa recta
  • It is concentrated as it descends in due to solute entry and loss of water
  • It is diluted as it ascends due to solute loss and gain of water
  • Resulting in little net dilution
  • Preventing loss of hyperosmolarity in medullary interstitial fluid
108
Q

Outline two mechanisms for controlling extracellular fluid osmolarity and sodium concentration

A
  • Osmoreceptor ADH system

- Thirst mechanism

109
Q

Where are osmoreceptor cells located and how does their activation cause increase ADH release?

A
  • Anterior hypothalamus near supraoptic nuclei
  • They shrink when osmolarity ([Na]) increase above normal
  • Which causes them to fire signal down pituitary stalk to posterior pituitary gland
  • Causing secretion of granular ADH into bloodstream
110
Q

How is ADH synthesised?

A
  • By magnocellular neurons in the supraoptic and paraventricular nuclei
111
Q

Where is the AV3V region located?

A
  • Anteroventral region of third ventricle
112
Q

Identify the structures of the AV3V region

A
  • Subfornical organ superiorly
  • Organum vasculosum inferiorly
  • Median preoptic nuclei (which connects to both organs as well as the supraoptic nuclei)
113
Q

Why can the subfornical organ and organum vasculosum respond to changes in osmolarity?

A
  • They lack the typical blood brain barrier

- Allowing for diffusion of ions from the blood into the brain tissue

114
Q

Outline the two cardiovascular reflexes involving in stimulating ADH release

A
  • Arterial baroreceptor reflexes
  • Cardiopulmonary reflexes
  • Which originate in high pressure regions (aortic arch and carotid sinus)
  • Afferent stimuli are carried by CN9 and CN10 to tractus solitarius
  • Which relays signals to hypothalamic nuclei controlling ADH synthesis and secretion
  • E.g. increased ADH secretion in haemorrhage
115
Q

Outline 3 additional factors that increase ADH secretion

A
  • Nausea
  • Hypoxia
  • Drugs: morphine, nicotine, cyclophosphoamide
116
Q

Outline three drugs that decrease ADH secretion

A
  • Alcohol
  • Clonidine
  • Haloperidol
117
Q

Outline 3 stimuli for thirst

A
  • Extracellular fluid osmolarity
  • Angiotensin II
  • Dryness of mouth
118
Q

Identify the three determinants of potassium excretion

A
  • Rate of potassium filtration
  • Rate of potassium reabsorption
  • Rate of potassium secretion
119
Q

Where is the majority of potassium reabsorbed?

A
  • PCT
120
Q

In which part of the loop of Henle does most potassium reabsorption take place?

A
  • Thick ascending part
121
Q

Identify the three main factors that control potassium secretion by the principal cells

A
  • Na+-K+ ATPase activity
  • Electrochemical gradient fro potassium secretion
  • Permeability of luminal membrane for potassium
122
Q

Which cells reabsorb potassium in severe potassium depletion?

A
  • Intercalated cells
123
Q

What is hypocalcaemic tetany?

A
  • Increased excitability of nerve and muscle cells
  • As a result of hypocalcaemia
  • Characterised by spastic skeletal muscle contractions
124
Q

How does plasma [H+] affect calcium binding to plasma proteins

A
  • Acidosis: Less calcium is bound to plasma proteins (possible role of denaturation?)
  • Alkalosis: More calcium bound to plasma proteins
125
Q

How does calcium excretion differ to other ions?

A
  • Excretion also occurs in faeces
126
Q

Outline the role of the parathyroid glands when extracellular [Ca2+] falls

A
  • Promote secretion of PTH
  • Which increases calcium resorption from bone
  • And stimulates intestinal resorption of calcium via Vitamin D
  • Elevating extracellular [Ca2+]
127
Q

Why is only 50% of plasma calcium filtered at the glomerulus?

A
  • The other 50% is bound to plasma proteins

- Or forms complex anions with phosphate

128
Q

Identify five factors that increase calcium excretion

A
  • Decreased PTH
  • Increased extracellular fluid volume
  • Increased blood pressure
  • Decrease plasma phosphate
  • Metabolic acidosis
129
Q

Identify two ways in which PTH regulates plasma phosphate concentration

A
  • High PTH increases bone resorption, releasing phosphate ions into extracellular fluid
  • High PTH decreases transport maximum of phosphate, decreasing tubular absorption and increasing excretion
130
Q

What is the primary site of magnesium reabsorption?

A
  • Loop of Henle
131
Q

Identify 3 factors that cause increased magnesium excretion

A
  • Increased extracellular magnesium concentration
  • Extracellular volume expansion
  • Increased extracellular fluid calcium concentration
132
Q

What are nonvolatile acids?

A
  • Acids produced from protein metabolism
  • That cannot be excreted by the lungs
  • So must be removed via the kidneys
133
Q

Outline the process of H+ secretion in the PCT

A
  • Secondary active secretion
  • Reabsorption of Na+ into cell
  • Provides energy for H+ secretion against a concentration gradient
134
Q

Outline the process of HCO3- reabsoprtion in the PCT

A
  • CO2 diffuses into tubular cells
  • Combines with water to form H2CO3 (catalysed by CA)
  • Which dissociates into HCO3- and H+
  • H+ secretion against a concentration gradient via secondary active secretion with sodium
  • HCO3- crosses basolateral membrane into renal interstitium
135
Q

Outline the process of H+ secretion in the DCT

A
  • Primary active transport

- H+ is transported through ATPase protein in intercalated cells

136
Q

Outline the phosphate buffer system

A
  • Depletion of HCO3-
  • So H+ combines with HPo42- to form H2PO4-
  • Which is excreted as NaH2PO4 in the urine
137
Q

Outline the ammonia buffer system

A
  • Glutamine enters epithelial cells
  • Metabolised to NH4+ and HCO3-
  • NH4+ is secreted into lumen by a counter transport mechanism with sodium
  • HCO3- is transported across basolateral membrane with sodium
138
Q

How does the ammonia buffer system differ in the collecting tubules?

A
  • Collecting ducts are permeable to NH3
  • Which diffuses into tubular lumen
  • And combines with secreted H+ to form NH4+
  • Which is eliminated in urine
139
Q

When does acidosis occur?

A
  • When ratio of HCO3- to CO2 decreases

- Decreasing pH

140
Q

What is the difference between metabolic and respiratory acidosis?

A
  • Metabolic: Decrease in HCO3-

- Respiratory: Increase in PCO2

141
Q

What is the affect of acidosis on the renal tubular fluids?

A
  • Decreased ratio of HCO3- to H+
  • Resulting in an excess of H+ in the tubule
  • Which combines with urinary buffers
  • HCO3- is reabsorbed
142
Q

When does alkalosis occur?

A
  • When ratio of HCO3- to CO2 increases

- Increasing pH

143
Q

What is the difference between metabolic and respiratory alkalosis?

A
  • Metabolic: Increase in HCO3

- Respiratory: Decrease in PCO2

144
Q

Outline the renal response to respiratory alkalosis

A
  • Decrease in PCO2 leads to a decrease in H+ secreted by renal tubules
  • Not enough H+ to react with HCO3- that is filtered
  • HCO3- that cannot react with H+ is excreted in urine
145
Q

Outline the mechanism of action of loop diuretics

A
  • Act on thick ascending limb
  • Combine with Cl- binding site on Na+/K+/2Cl-
  • Inhibit Na+ reabsorption
  • Also have vasodilatory effect
146
Q

Identify two loop diuretics

A
  • Furosemide

- Bumetanide

147
Q

Loop diuretics increase excretion of [A] and [B] and decrease excretion of [C]

A
  • [A] Ca2+
  • [B] Mg2+
  • [C] Uric acid
148
Q

Identify unwanted effects of loop diuretics

A
  • Hypovolaemia and hypotension
  • Hypokalaemia and metabolic acidosis
  • Hypomagnesaemia and hyperuricaemia (gout)
  • Hearing loss
  • Allergic reactions
149
Q

Outline the mechanism of action of thiazide diuretics

A
  • Act on DCT
  • Bind to Cl- site on Na+/Cl- co transport system
  • Inhibiting its action
  • Resulting in natriuresis with loss of sodium and chloride into urine
  • Vasodilatory action (useful in hypertension)
150
Q

Why are thiazide diuretics advantageous over loop diuretics in older patients?

A
  • They reduce Ca2+ excretion

- So reduced bone resorption in older patients at risk of osteoporosis

151
Q

Identify unwanted effects of thiazide diuretics

A
  • Increased urinary frequency
  • Erectile dysfunction
  • Impaired glucose tolerance (activation of KATP channels)
  • Hyponatraemia
  • Hypokalaemia (adverse drug reaction which precipitates encephalopathy)
  • Allergic reactions
152
Q

Identify two thiazide diuretics and three related drugs

A
  • Bendroflumethiazide
  • Hydrochlorothiazide
  • Chlortalidone
  • Indapamide
  • Metolazone
153
Q

Identify two aldosterone antagonists

A
  • Spironolactone

- Eplerenone

154
Q

What is the active metabolite of spironolactone

A
  • Canrenone
155
Q

Identify unwanted effects of aldosterone antagonists

A
  • Fatal hyperkalaemia
  • GI disturbances
  • Gynaecomastia (actions on progesterone/androgen receptors)
156
Q

How is cardiac toxicity of hyperkalaemia counteracted?

A
  • Intravenous calcium gluconate

- Glucose + Insulin (to shift K+ into cell)

157
Q

Outline the mechanism of action of triamterene and amiloride

A
  • Act on collecting tubules and ducts
  • Inhibit Na+ reabsorption by blocking luminal sodium channels
  • Decreases K+ excretion
158
Q

Identify the unwanted effects of triamterene and amiloride

A
  • Hyperkalaemia
  • GI disturbances
  • Kidney stones (triamterene only)
  • Skin reactions
159
Q

Identify a carbonic anhydrase inhibitor

A
  • Acetazolamide
160
Q

Identify the mechanism of action of carbonic anhydrase inhibitors

A
  • Acts on PCT
  • Increases excretion of bicarbonate
  • With accompanying Na+, K+ and water
  • Resulting in an increased flow of alkaline urine and metabolic acidosis
161
Q

Identify a use of acetazolamide

A
  • Glaucoma for reduction of aqueous humor formation
162
Q

Identify an osmotic diureitc

A
  • Mannitol
163
Q

Identify the mechanism of action of mannitol

A
  • Reduces passive water reabsorption
164
Q

What is diabetic nephropathy?

A
  • Manifestation of diabetic microvascular disease

- Involving renal arterioles and glomeruli

165
Q

Outline the pathophysiology of diabetic nephropathy

A
  • Glucose combines with amino acids forming advanced glycosylation end products
  • Which accumulate in tissues by cross-linking with collagen molecules
  • Stimulation of mesangial cell proliferation and matrix production
  • Which produces thicker more permeable glomerular basement membrane
166
Q

What causes glomerular hyperperfusion and hyperfiltration in diabetic nephropathy?

A
  • Defective autoregulation and albumin leakage
167
Q

Identify the clinical features of diabetic nephropathy

A
  • Microalbuminuria (30-300 mg/day)
  • Followed by more severe proteinuria
  • Commonest cause of end-stage kidney disease
168
Q

Which type of diabetes is most associated with the development of diabetic nephropathy?

A
  • Type 1

- With a clear relationship between duration of diabetes (15 years) and histological changes

169
Q

Identify the morphological changes in diabetic nephropathy

A
  • Thickening of glomerular basement membrane
  • Depletion of podocytes
  • Increase in mesangial matrix
  • Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) of collagen and other matrix proteins
170
Q

How is diabetic nephropathy managed?

A
  • Lifestyle changes
  • Control of hypertension and poor metabolic regulation
  • ACE inhibitors and ARAs following microalbuminuria
  • Paricalcitol (vitamin D receptor activator)
171
Q

Identify three clinical findings that suggest acute pyelonephritis

A
  • Fever
  • Loin pain
  • Tenderness
172
Q

Outline the structural changes in acute pyelonephritis

A
  • Renal cortical abscesses
  • Steaks of puss
  • Infiltration of leucocytes in tubular lamina
173
Q

What is the treatment for acute pyelonephritis

A
  • Amoxicillin

- Co-amoxiclav and ciprofloxacin in resistant organisms

174
Q

Outline the basic principles of haemodialysis

A
  • Blood is pumped through semi-permeable membrane (dialyser)
  • Blood comes into contact with dialysate
  • Causing diffusion of molecules down their concentration gradient
175
Q

What is the blood flow during dialysis and the flow of dialysate?

A
  • Blood: 200-300 ml/min

- Dialysate: 500 ml/min

176
Q

What is the best way to achieve a blood flow of 200ml for dialysis?

A
  • Arteriovenous fistula
  • Usually the radial or brachial artery and the cephalic vein
  • Resulting in distension and thickening of the vein
177
Q

What is the frequency and duration of haemodialysis?

A
  • 4-5 hours three times a week

- Optimal dialysis is adjusted to individual patient needs

178
Q

Why are patients anticoagulated during haemodialysis tretment?

A
  • Contact with foreign surfaces activates the clotting cascade
179
Q

Identify complications of haemodialysis

A
  • Hypotension
  • Anaphylactic reactions to ethylene oxide used to sterilise dialysers
  • Hard water syndrome (nausea and vomiting)
  • Haemolytic reactions
  • Air embolism
180
Q

Outline the basic principles of peritoneal dialysis

A
  • A tube is placed in peritoneal cavity through AAW
  • Dialysate is run into peritoneal cavity
  • Urea, creatine and phosphate pass into dialysate down concentration gradients
  • Water is attracted into peritoneal cavity by osmosis
  • The fluid is changes regularly to repeat the process
181
Q

What is the role of glucose or polymer (icodextrin) in peritoneal dialysis?

A
  • Determines osmolarity of dialysate
182
Q

Outline the main complication of peritoneal dialysis

A
  • Bacterial peritonitis
  • With abdominal pain, guarding, rebound tenderness
  • And a cloudy peritoneal effluent (diagnostic)
183
Q

Identify a second complication of peritoneal dialysis

A
  • Constipation
184
Q

Outline the Human Tissue Act 2004

A
  • Permits opt in donation post mortem
  • Allows family members to refuse if donor not on ODR
  • Permits live organ donation to be target to specific individuals
  • Makes paid donations illegal
  • Allows 12 years olds and above to make their own decision
185
Q

What does the Amends Organ Donation Bill state?

A
  • Person concerned is deemed to have consented to transplantation
  • Unless a person who stands in a qualifying relationship to the person provides information
  • That would lead to a reasonable person to conclude that the person concerned would not have consented.
186
Q

Identify factors for assessing allocation policies in organ donation

A
  • Patient benefit
  • Transparency
  • Equity of access
  • Geographical equity
187
Q

What is motivational interviewing?

A
  • Collaborative conversation
  • That elicits and strengthens peoples good motivations
  • For making lifestyle and behaviour changes
188
Q

Identify four aspects within the spirit of motivational interviewing

A
  • Compassion
  • Collaborative
  • Evoking
  • Supporting autonomy
189
Q

What is sustain talk?

A
  • Patients talk about why they should stay the same

- Helps to identify obstacles the individual should overcome

190
Q

What is change talk?

A
  • Patients talk about changing
  • Including their reasons, motivations and self-efficacy
  • Helps an individual move towards change
191
Q

Identify four skills required for motivational interviewing

A
  • Open questions
  • Affirmations
  • Reflective listening
  • Summarising
192
Q

Identify four reasons why motivational interviewing is important

A
  • Understand patient perspective
  • Builds relationship with patients
  • Helps individuals take more responsibility for their health
  • May assist individuals in self-management

Semester 4: Nutrition and Metabolism (17 decks)

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