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Block 1 > Anatomy and Physiology of the Kidney > Flashcards

Anatomy and Physiology of the Kidney Flashcards

1
Q

What are the three main processes performed by the nephron?

A

Filtration

Reabsorption

Secretion

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2
Q

What makes up the renal corpuscle?

A

Bowman’s capsule

Glomerulus capillaries

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3
Q

What specialisations do simple squamous cells have and where are they found in the kidney?

A

Allow passive movement
Small intracellular volume - less need for mitochondria for energy or protein

Bowman’s capsule

Thin descending limb

Thin ascending limb

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4
Q

What specialisations do simple cuboidal cells have and where are they found in the kidney?

A

Large intracellular volume - mitochondria for energy and protein for transporters.
Good for reabsorption

Thick ascending limb of loop of Henle
Distal tubule

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5
Q

What specialisations to simple columnar cells have and where are they found in the kidney?

A

Large intracellular volume
High organelle density for energy reserves.
Good for motility, absorption and procession.

Found along the collecting duct.

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6
Q

What are the four functions of the kidney?

A

Regulation of body fluid volume

Regulation of body fluid composition

Excretion of metabolic waste and toxins

Endocrine functions

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7
Q

What two parts make up the uriniferous tubule?

A

Nephron

Collecting duct

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8
Q

Name the four parts of the nephron.

A

Renal corpuscle

Proximal tubule

Loop of Henle

Distal tubule

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9
Q

Describe the blood supply of the kidney

A

Renal artery –> segmental artery –> interlobar arteries –> arcuate arteries –> interlobular arteries –> afferent and efferent arterioles

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10
Q

What is the main extracellular fluid cation and anion?

A

Cation - sodium

Anion - chloride

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11
Q

What is the main intracellular cation and anion?

A

Cation - potassium

Anion - phosphate

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12
Q

What are the five human tissue types?

A

Epithelia, muscle, connective tissue, blood, nervous tissue

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13
Q

What makes up the uriniferous tubule?

A

Nephron and collecting duct

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14
Q

What is the name of the capillaries around the nephron (low pressure)?

A

Peritubular capillaries - for reabsorption and secretion

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15
Q

What are the capillaries in Bowman’s capsule called?

A

Glomerular capillaries - high pressure for filtration

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16
Q

What makes up the renal corpuscle? (2)

A

Glomerulus

Bowman’s Capsule

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17
Q

Name the capillaries in the medulla around the Loop of Henle?

A

Vasa recta

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18
Q

What is the outer layer of Bowman’s capsule called?

What is its purpose?

What epithelial cell type is it made of?

A

Parietal layer

Containment

Simple squamous

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19
Q

What is the inner layer of Bowman’s capsule called?

What is its purpose?

What epithelial cell type is it made of?

A

Visceral layer

Filtration

Modified simple squamous (podocytes)

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20
Q

Name the layers of the glomerular filtration barrier (3)

A

Glomerular capillary endothelium (fenestrated)

Basement membrane (negative charge)

Epithelium (podocytes)

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21
Q

How does the filtration barrier limit the passage of certain substances?

A

Glomerular capillary endothelium - size

Basement membrane - repels -ve charges

Epithelium (podocytes) - shape

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22
Q

What two things are excluded from filtrate?

A

Blood cells

Plasma proteins

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23
Q

Where does the majority of water, sodium, chloride, amino acid, and glucose reabsorption take place?

A

Proximal tubule

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24
Q

Name the functions of the proximal tubule

A

Reabsorb - water, sodium, chloride, amino acids, glucose.

Secrete - drugs and waste molecules

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25
Q

What type of cells are found in the proximal tubule?

A

Simple cuboidal cells with microvilli (brush border to increase surface area).

Cuboidal cells have larger intracellular space - room for mitochondria to make transport proteins

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26
Q

Is the thin descending limb permeable or impermeable to water?

A

Permeable

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27
Q

What type of epithelium does the thin descending limb have?

A

Simple squamous epithelium

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28
Q

Is the thin ascending limb permeable or impermeable to water?

A

Impermeable

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29
Q

What type of epithelium does the thin ascending limb have?

A

Simple squamous epithelium

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30
Q

Do active or passive movements take place in the thin descending and ascending limbs?

A

Passive

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31
Q

Is the thick ascending limb permeable or impermeable to water?

A

Impermeable

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32
Q

What type of epithelial cell does the thick ascending limb have?

A

Simple cuboidal

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33
Q

What takes place in the thick ascending limb?

A

Active reabsorption of sodium and other solutes

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34
Q

What type of epithelial cells are found in the distal tubule?

A

Simple cuboidal

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35
Q

Is the distal tubule permeable or impermeable to water?

A

Variable depending on the presence of ADH

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36
Q

What forms the juxtaglomerular apparatus?

A

Macula densa

Extraglomerular mesangial cells (Lacis cells)

Granualar/Juxtaglomerular cells in afferent arteriole

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37
Q

Name the specialist cells in the early distal tubule at the JGA

A

Macula densa

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38
Q

What solutes does the macula densa detect?

A

Sodium

Chloride

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39
Q

Is the collecting duct permeable or impermeable to water?

A

Variable depending on the presence of ADH

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40
Q

What type of cells are found in the collecting duct?

A

Simple columnar

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41
Q

Define osmosis

A

The passive transport of water across a semipermeable membrane down a concentration gradient

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42
Q

What is the main osmotically active electrolyte in extracellular fluid?

A

Sodium

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43
Q

What is the main osmotically active electrolyte in intercellular fluid?

A

Potassium

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44
Q

What hormone is produced in the kidney in a hypoxic state?

What does it do?

A

Erythropoietin

Stimulates production of RBC precursors in bone marrow

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45
Q

Which enzyme is produced in the kidney to convert the inactive precursor of vitD to its active form?

A

1a-hydroxylase

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46
Q

How do you formulate the urinary excretion rate?

A

Filtration rate + secretion rate - reabsorption rate

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47
Q

What is glomerular filtration rate?

A

The volume of filtrate formed by all the nephrons in both kidneys per unit time.

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48
Q

What is the equation for GFR

A

GFR = Kf x NFP

Kf = glomerular capillary filtration coefficient

NFP = net filtration pressure

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49
Q

What determines the glomerular capillary filtration coefficient (Kf)

A

Surface area for filtration (how many nephrons available)

Hydraulic conductivity (permeability) of the filtration barrier (3 layers of renal corpuscle)

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50
Q

What increases eGFR?

arterioles

A

AA dilation and/or EA constriction

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51
Q

What decreases eGFR?

arterioles

A

AA constriction and/or EA dilation

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52
Q

Name 3 substances that have an affect on glomerular pressure

A

Angiotensin II - constricts EA
Prostaglandins - vasodilate AA
Noradrenaline - vasoconstrict AA

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53
Q

Why do peritubular capillaries favour reabsorption?

A

High oncotic pressure (concentrated plasma proteins) and low capillary hydrostatic pressure (fluid on vessel walls)

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54
Q

What are the two mechanisms of autoregulation of eGFR?

A

Myogenic response

Tubuloglomerular feedback

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55
Q

At which vertebral level is the hilum of the kidney?

A

L1

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56
Q

Which vertebral levels does the kidney normally sit between?

A

T11 - L2/3

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57
Q

Which paracrine factor is released in HTN in the tubuloglomerular feedback system?

What does this cause?

A

Adenosine

Constriction of AA smooth muscle

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58
Q

Which endocrine factor is released in hypotension in the Tubuloglomerular feedback system?

Which cells is it released from?

What does it cause?

A

Renin

Gramilin cells

Constriction of EA muscle

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59
Q

What does low quantities of sodium chloride in the macula densa cause?

A

Secretion of renin.

Afferent arteriole dilation

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60
Q

What type of epithelium is found on the lining of the bladder?

A

Transitional epithelium

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61
Q

Which nerve supplies the urinary sphincters?

A

Pudendal nerve S2-4

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62
Q

Describe the type of muscle in the urinary sphincters

A

Internal sphincters - smooth muscle (involuntary)

External sphincters - skeletal muscle (voluntary)

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63
Q

Where do sensory nerves from the superior part of the bladder (on the peritoneum) travel to?

A

T12-L2

Travel to CNS with sympathetic nerves

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64
Q

Where do sensory nerves inferior to the peritoneum travel to?

A

S2-4

Travel to CNS with parasympathetic nerves

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65
Q

How do NSAIDs reduce eGFR?

A

Inhibit prostaglandin production - AA become constricted - reduces eGFR

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66
Q

How do ACEi/ARB reduce eGFR?

A

Prevent production/action of angiotensin II - EA become dilated - reduces eGFR

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67
Q

Where do carbonic anhydrase inhibitors have their site of action?

A

Proximal tubule

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68
Q

Where do osmotic diuretics have their site of action?

A

Proximal tubule and descending loop of Henle

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69
Q

Where do loop diuretics have their site of action?

A

Ascending loop of Henle

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70
Q

Where do thiazides have their site of action?

A

Early distal tubule

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71
Q

Where do potassium sparing diuretics have their site of action?

A

Late distal tubule and collecting duct.

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72
Q

Name the five classes of diuretics

A 
Potassium sparing diuretics
Osmotic diuretics
Loop diuretics
Carbonic anhydrase inhibitors
Thiazide diuretics
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73
Q

How do loop diuretics cause hypokalaemia?

A

Increased delivery of Na+ to distal tubule –> increased uptake of Na+ in distal tubule –> secretion of K+.

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74
Q

How to carbonic anhydrase inhibitors lead to metabolic acidosis?

A

Prevents absorption of HCO3- into blood –> less alkaline in blood –> more acidic environment in blood.
Prevents secretion of H+ molecules –> more intra/extracellular.

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75
Q

Describe the location of the uriniferous tubule in relation to the cortex and medulla of the kidney

A

Cortex - mainly renal corpuscles, proximal tubule, distal tubule

Medulla - mostly LoH and collecting ducts

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76
Q

What factor determines if a nephron is cortical or juxtamedullary?

A

The position of the renal corpuscle

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77
Q

Where can arcuate arteries be found?

A

Running along the corticomedullary junction

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78
Q

Name the 2 capillary beds that blood passes through in the kidney

A

Glomerular capillaries

  • high pressure
  • filtration

Peritubular capillaries

  • low pressure
  • reabsorption/secretion
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79
Q

What type of cells provide support between the glomerular capillary loops?

A

Mesangial cells

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80
Q

What 5 things are reabsorbed in the PCT?

A

Sodium

Water

Chloride

Amino acids

Glucose

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81
Q

What is the net result of filtrate passing through the loop of Henle?

A

Produce concentrated urine

Hyperosmolar interstitium in medulla

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82
Q

What surrounds the collecting duct of a nephron?

What is the key role of the collecting duct?

A

Medullary interstitium with a high concentration of solutes

Produces a concentration gradient

Key role in regulating degree of urine concentration

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83
Q

In a typical male, what % of body weight is water?

A

60%

42 litres

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84
Q

42 litres total in a typical male, how much is intracellular and extracellular?

A

Intracellular - 28 litres

Extracellular - 14 litres

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85
Q

What are the 2 main compartments of extracellular fluid (ECF)?

A

Interstitial fluid - surrounds the cells

Plasma - non-cellular component of blood

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86
Q

What separates intracellular and extracellular fluid?

A

Semipermeable membranes

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87
Q

What is the main difference between plasma and interstitial fluid?

A

Plasma has proteins in it

Capillary membrane is highly permeable to water and electrolytes but not to most plasma proteins

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88
Q

What type of anaemia can be seen in kidney disease?

Explain the pathophysiology

A

Normochromic normocytic

Kidneys release erythropoietin in respons to hypoxia

Erythropoietin is a growth factor that stimulates to production of hematopoietic stem cells (RBC precursors) in bone marrow

Fewer RBCs being made = anaemia

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89
Q

What 5 factors can decrease tissue oxygenation?

A

Low blood volume

Anemia

Low Hb

Poor blood flow

Pulmonary disease

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90
Q

Which 2 muscles are posterior relations of the kidney?

A

Psoas major

Quadratus lumborum

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91
Q

Is the kidney inter or retro peritoneal?

A

Retroperitoneal

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92
Q

What is Morrison’s pouch?

A

Space between liver and R kidney.

Potential space for infection to spread into when lying down (gravity dependent)

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93
Q

What space communicates across the midline between both kidneys, and therefore is a potential route of infection spread?

A

Renal fascia space

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94
Q

From closest to furthest, which 3 fats/fascia surround the kidney?

A

Perinephric fat

surrounded by Renal Fascia

Paranephric fat

surrounded by Psoas Fascia

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95
Q

What does the kidney develop from in utero?

A

Metanephros (intermediate mesoderm)

Ureteric bud

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96
Q

Describe the formation of the blood supply to the kidney

A

Kidneys start at lower vertebral level, have to ascend

Gets new blood supply as it ascends

Can cause problems

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97
Q

What is a polar renal artery?

A

Kidney with 2 arteries

1 is a remnant of kidney being at a lower vertebral level

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98
Q

What is an aberrant renal artery?

A

A second renal artery that blocks the ureter

Can cause decreased renal function

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99
Q

What is a horseshoe kidney?

What problem can it cause?

A

Joining of the inferior poles of both kidneys

Joins under the IMA - potential site of restricted blood flow

100
Q

What is the difference between a bifid and duplicate ureter?

A

Bifid - 2 ureteric openings at the kidney, join together before reaching the bladder

Duplicate - 2 ureters and 2 openings to the bladder

101
Q

What does the bladder develop from in utero?

A

Anterior part of cloaca with allantois attached

102
Q

What is the purpose of the allantois in utero?

A

Formation of blood cells

103
Q

List 3 problems that the allantois can cause in adults

A

Urachal cysts - incomplete closure of the allantois causing open spaces

Urachal sinus - open space from the umbilicus down towards the bladder, not all the way down

Urachal fistula - complete opening of the allantois

104
Q

Describe the arterial blood supply to the right kidney

A

The right renal artery is longer, and crosses the vena cava posteriorly

105
Q

Do the renal arteries arise above or below the SMA?

A

Immediately below

106
Q

Which other vein joins the L renal vein?

A

Left testicular/ovarian veins

Only on the L side

The R testicular/ovarian veins drain directly into the IVC

107
Q

Describe the referred pain pattern of a renal calculus

A

Shifting ‘loin-groin’ pain

108
Q

How do visceral sensory nerves from the ureters travel to the CNS?

A

Alongside sympathetic nerves

109
Q

Where are the 3 common places for a renal stone to get stuck?

A

Pelvic-ureteric junction (PUJ)

Where the ureter crosses the iliac vessels

Vesico-ureteric junction (VUJ)

110
Q

What is the major differential/concern for an elderly patient presenting with presumed left sided renal colic?

A

Ruptured AAA

111
Q

Where do the ureters enter the bladder?

A

At the level of the ischial spines

Vesico-ureteric junction

112
Q

What cell type lines the bladder?

A

Transitional epithelium (urothelium)

113
Q

Where is the trigone of the bladder?

A

Bladder wall between the 2 ureters and urethra

114
Q

What prevents urine reflux during micturition?

A

Vesico-ureteric valve (thickening of detrusor muscle)

115
Q

List the 3 male sphincters

A

Internal urethral sphincter

External urethral sphincter

Compressor urethrae

116
Q

List the ?4 female sphincters

A

Internal urethral sphincter

External urethral sphincter

Compressor urethrae

Sphincter urethrovaginalis

117
Q

Which nerve are most urinary sphincters innervated by?

A

Pudendal nerve S2-4

118
Q

Are the internal and external urethral sphincters smooth or skeletal muscle?

A

Internal urethral sphincter

  • smooth muscle
  • involuntary

External urethral sphincter

  • skeletal muscle
  • voluntary
119
Q

What is the source of the bladder’s blood supply?

A

Internal iliac artery

120
Q

What tissue layers does a suprapubic catheter pass through to get to the bladder?

A

Skin

Subcutaneous tissue,

Superficial fascia

Linea alba (midline, remember we are below umbilicus)

Tranversalis fascia

Parietal peritoneum

Bladder wall

121
Q

Which 2 ligaments support the bladder in females?

A

Pubo-vesical ligament

Levator ani

122
Q

Which 2 ligaments support the bladder in males?

A

Levator ani

Pubo-prostatic ligament

123
Q

What is a cystocele?

A

Protruding bladder caused by weakness of bladder support in females

124
Q

Where does the top of the bladder send its sensory nerves?

Why is this?

How do nerves on top of the bladder get back to the CNS?

A

T12-L2

Top of the bladder is covered in peritoneum

Gets back to the CNS with sympathetic nerves

125
Q

Where does the bulk of the bladder send its sensory nerves?

Why is this?

How do nerves around the bladder get back to the CNS?

A

S2-4

Bladder is retorperitoneal

Gets back to CNS with parasympathetic nerves

126
Q

What is the pelvic pain line?

A

An organ in the pelvis is said to be “above the pelvic pain line” if it is in contact with the peritoneum

127
Q

What nerves allow us to pee?

What do they do?

A

Parasympathetic nerves S2-4

Contract detrusor muscle

Relax internal urethral sphncter

128
Q

What nerve tell us to stop peeing?

What do they do?

A

Sympathetic L1-2

Constricts internal urethral sphincter

Relaxes detrusor muscle

129
Q

What role do somatic nerves splay on micturition?

A

Tell us to stop peeing

Pudendal nerve (S2-4)

Contracts external urethral sphincter

130
Q

List the 3 categories of lower urinary tract symptoms (LUTS)

Give some examples in each

A

Storage LUTS

Voiding LUTS

Post-micturition LUTS

131
Q

Give some examples of storage LUTS

A

Incontinence

Urgency

Frequency

Nocturia

132
Q

Give some examples of voiding LUTS

A

Poor stream

Hesitancy

Dysuria

Double voiding

Retention

133
Q

Give an example of post-micturition LUTS

A

Terminal dribbling

134
Q

Define urinary incontinence

A

Involuntary loss of urine in sufficient amount or frequency to constitute a social and/or health problem

135
Q

Give 6 types of incontinence

A

Stress

Urge

Overflow

Functional

Continuous

Childhood

136
Q

Describe stress incontinence

A

Pressure inside the bladder becomes greater than the strength of the urethra to stay closed

Involuntary leaking on effort or exertion or on sneezing or coughing

Middle aged females

Males post-prostate surgery

137
Q

Describe urge incontinence

A

Involuntary urine leakage accompanied/preceded by urgency

Overactive bladder

Commonest cause of incontinence >50

138
Q

Describe overflow incontinence

A

Prolonged problems with bladder emptying lead to chronic retention and detrusor failure

Most often men

139
Q

Describe functional incontinence

A

Consequence of something not involving the urinary tract

  • mobility
  • dementia
  • diuretics
140
Q

Describe urodynamics

A

Study of pressure and flow during storage, transport and expulsion of urine in the (lower) urinary tract

Comes up as a graph of normal flow vs. patient flow

141
Q

Describe outflow cystometry

A

Urethral catheter in bladder

Transducer in rectum

Fill bladder will fluid, record pressures in bladder and rectum, bladder emptied and pressures recorded.

Gives force from detrusor muscle

142
Q

What drugs can be given for urge incontinence/overactive bladder?

Describe their MoA

Give side effects

A

Anticholinergics
- Oxybutynin

Competitively inhibits M2 M3 muscarinic receptors on the detrusor muscle, blocking the action of Ach.

Parasympathetic nerves

Reduces detrusor responsiveness

SIDE EFFECTS
Dry mouth
Dry eyes
Constipation
Blurred vision/glaucoma
Fatigue
Retention
143
Q

What drugs can be given for urinary retention and BPH?

Describe their MoA

Give side effects

A

Doxazosin (selective a1 blocker)

Blocks a1 receptors on sympathetic neurons on bladder neck, urethra and prostate

Blocks noradrenaline

Inhibits contraction of smooth muscle, relaxes muscles facilitates urinary flow

SIDE EFFECTS
Nausea 
Dry mouth
Fatigue
Constipation
144
Q

What can cause urinary retention?

A

BPH

Prostate CA

Prostatitis

Haematuria

Tumours

Stones

145
Q

Describe BPH

Give symptoms

A

Enlarged prostate blocking urethra

SYMPTOMS
Hesitancy
Straining
Weak flow
Stop-start
Nocturia
Incontinence
Feeling of incomplete emptying
146
Q

Describe the international prostate symptom score

A

7 symptom questions

  • frequency
  • nocturia
  • urgency
  • hesitancy
  • poor stream
  • intermittency
  • incomplete emptying

1 QoL question

147
Q

What examinations/investigations would you do for BPH?

A

Prostate symptom score

PSA

Abdo exam

DRE

Transrectal USS

148
Q

What drug would you give in BPH management?

A

Doxazosin

selective a-1 blocker

149
Q

In which zone of the prostate do most cancers start?

A

Peripheral zone (outer zone furthest away from urethra)

150
Q

Which zone of the prostate gets bigger with age and is usually responsible for BPH?

A

Transition zone (surrounds the urethra)

151
Q

Describe the process of renal stone formation

A

Crystalline growth

Has to be stasis of urine for calcium oxalate crystal to aggregate

152
Q

Describe struvite stones

What causes them?

A

Form in alkaline urine that contain ammonia

Cause is urinary infection by urea-splitting bacteria

Urea —-(urease)—> CO2 + ammonia

NH3 increases urine pH

Precipitation of magnesium, ammonium, phosphate

Often forms staghorn stone

153
Q

Describe uric acid stones

A

Accumulation of urate from purine metabolism

154
Q

Describe a typical presentation of renal colic

A

Loin to groin pain

Haematuria

Vomiting

Irritative voiding symptoms

155
Q

Urinary excretion rate =

A

Filtration rate + secretion rate - reabsorption rate

156
Q

What is the net filtration pressure?

A

The sum of the pressures acting across the filtration barrier (Starling forces)

Sum of hydrostatic pressures (on walls)

Sum of the colloid osmotic (oncotic) pressures (proteins in blood and osmosis)

157
Q

What is the equation for net filtration pressure (NFP)?

A

Pg - Pb - IIg + IIb

Pg = glomerular hydrostatic pressure

Pb = bowman’s capsule hydrostatic pressure

IIg = glomerular colloid oncotic pressure (proteins pulling back water)

IIb = bowman’s capsule colloid osmotic pressure (should be 0)

158
Q

If someone has urinary tract obstruction, which part of the net filtration formula will be affected?

A

Pb - bowman’s capsule hydrostatic pressure

159
Q

What determines glomerular hydrostatic pressure (Pg)?

A

BP

Afferent arteriole resistance

Efferent arteriole resistance

160
Q

Why is Pg the most important pressure in maintain GFR?

A

Most physiological regulation of GFR occurs due to changes in glomerular hydrostatic pressure (PG)

Can vary PG independently of arterial pressure by varying the resistance of the afferent & efferent arterioles

161
Q

What does angiotensin II do to net filtration pressure?

A

Preferentially constricts efferent arteriole

Increases Pg (glomerular hydrostatic pressure)

162
Q

What do prostaglandins and atrial natriuretic peptide (ANP) do to net filtration pressure?

A

Vasodilate afferent arteriole

Increases Pg (glomerular hydrostatic pressure)

163
Q

What do NA, adenosine and endothelin do to net filtration pressure?

A

Vasoconstrict afferent arteriole

Reduces Pg (glomerular hydrostatic pressure)

164
Q

Why do peritubular capillaries favour reabsorption?

A

The capillary hydrostatic pressure is lower

Colloid osmotic pressure in the capillaries is higher

Net force of pressures wants to go back into capillaries

165
Q

What are the 2 mechanisms of autoregulation of GFR

A

Myogenic response

Tubuloglomerular feedback

166
Q

Define a myogenic response

A

Inherent ability of smooth muscle in afferent arterioles to respond to changes in vessel circumference by contracting or relaxing

167
Q

Outline the myogenic autoregulation response in the kidney

A 
Increase in arterial blood pressure
↓
Increased renal blood flow and increased GFR
↓
↑stretch of afferent arteriole (AA) smooth muscle cells 
↓
Opens Ca2+ channels
↓
Reflex contraction of AA smooth muscle
↓
Vasoconstriction of AA
↓
↑Resistance to flow
↓
Prevents changes in renal blood flow & GFR
168
Q

Outline the tubuloglomerular feedback system in the kidney

A

Tubuloglomerular feedback mechanism links changes in [NaCl] in tubule lumen to control of own afferent arteriole resistance (glomerulus) in same nephron

Utilises juxtaglomerular apparatus (JGA)

169
Q

Which cells detect changs in NaCl?

Where are they found?

A

Macula densa cells

Early part of the dista tubule

170
Q

Describe the tubuloglomerular feedback in the kidney in increased BP

A 
Increase in arterial blood pressure (BP)
↓
Increased renal blood flow and increased GFR
↓
Increased [NaCl] delivered to macula densa cells
↓
Release of paracrine factors (e.g. adenosine)
↓
Constriction of AA smooth muscle
↓
Vasoconstriction of AA
↓
↑Resistance to flow
↓
Restores renal blood flow & GFR
171
Q

Describe the tubuloglomerular feedback in the kidney in reduced BP

A 
Decrease in arterial blood pressure (BP)
↓
Decreased renal blood flow and Decreased GFR
↓
Decreased [NaCl] delivered to macula densa cells
↓
Release of renin 
↓
Increase of angiotensin II
↓
Constriction of efferent arterioles
↓
Restores renal blood flow & GFR
172
Q

What does proteinuria/albuminuria indicate damage to?

A

Filtratation barrier

Strong association between proteinuria and rate of disease progression in CKD

173
Q

Define renal clearance

A

The volume of plasma from which a substance is completely cleared by the kidneys per unit time

174
Q

What is the equation for renal clearance?

A

Clearance (ml/min) =

V (ml/min) X U (mg/ml)

OVER

P ( mg/ml)

V - urine production
U - substance concentration in urine
P - substance concentration in plasma

175
Q

Which substance is filtered, not reabsorbed or secreted and is egual to GFR?

176
Q

How is urea handled by the kidney?

How does this reflect GFR?

A

Filtered, partially reabsorbed

Less than GFR

177
Q

How is creatanine handled by the kidney?

How does this reflect GFR?

A

Filtered and secreted

Greater than GFR

178
Q

How is creatanine made?

What can affect creatinine?

A

Formed from the breakdown of creatine, skeletal muscle component

Age
Sex
Muscle mass
Diet
Ethnicity 
Malnutrition
179
Q

Why is creatinine clearance not a suitable measure of renal function/GFR?

A

Requires 24hr urine collection - compliance, time, reliability

Small amount of secretion of creatinine means GFR tends to be overestimated

180
Q

Which 3 tests are routinely used to assess renal function?

A

Serum urea

Serum creatinine

eGFR

Single blood test

181
Q

What is urea?

What happens to it in the kidney?

What can affect urea?

A

Nitrogen containing metabolic waste product from the metabolism of proteins

Filtered, partially reabsorbed

Dehydration will mean more urea is reabsorbed

182
Q

List 4 things that can increase urea production

A

High protein diet

Increased catabolism (trauma, cancer)

GI bleed

Drugs (corticosteroids, tetracyclines)

183
Q

List 2 things that reduce urea elimination

A

Renal disease that causes a reduction in GFR

Poor renal blood flow (hypotension, dehydration)

184
Q

When analysing serum urea, what does it need to be compared to?

A

Compare to serum creatinine

If both have doubled, likely fall in GFR

If urea is disproportionately higher, think:
Dehydration
High protein
GI bleed
Catabolic state
185
Q

Why is creatinine not a useful tool to detect renal function on its own?

A

You can lose ~50% of renal function (GFR) and yet still appear to have a serum creatinine that lies within the ‘normal’ range

186
Q

What factors determine eGFR?

A

Serum creatinine

Age

Sex

Ethnicity

187
Q

Give some signs and symptoms of hypovolaemia

A

Symptoms

  • thirst
  • dizziness on standing
  • confusion

Signs

  • low JVP
  • weight loss
  • dry mucous membranes
  • reduced skin turgor
  • reduced urine output
188
Q

Give some signs and symptoms of hypervolaemia

A

Symptoms

  • ankle swelling
  • breathlessness

Signs

  • raised JVP
  • oedema
  • weight gain
  • hypertension
189
Q

What is the minimum obligatory urine production per day to excrete waste solutes?

A

500mls day

190
Q

Why can we alter water excretion independently of solute excretion?

A

If you drink large volumes of water, the amount of solutes excreted remains unchanged

This allows plasma osmolarity to remain constant

191
Q

If someone drinks a lot of water, will the osmolarity of urine be more or less than plasma?

A

Osmolarity will be less - more water is excreted compared to solutes

Can excrete water independently of solutes

192
Q

What is the formula for urine osmolarity?

A

Osmoles excreted/day (600mOsm) = urine osmolarity (mOsm/L) X urine output (L)

Osmolarity and urine output can change - figures can be different, as long as 600mOsm is excreted every day

193
Q

What is the maximum concentration of urine?

A

1200 mOsm/L

Therefore, typical obligatory urine volume = 0.5L / day

194
Q

What can cause increased water excretion?

Polyuria

A

Excessive water ingestion

Inability to concentrate urine (tubular damage, diabetes insipidus)

195
Q

What can cause increased solute excretion?

Polyuria

A

Diuretics (or failure to reabsorb sodium)

Glycosuria (diabetes)

196
Q

What can cause decreased water/solute excretion?

A

Dehydration

Low extracellular volume

Poor renal perfusion

197
Q

What does water reabsorption in the collecting ducts require?

A

Insertion of water channels (aquaporins) regulated by ADH

An osmotic gradient generated by the countercurrent system in the loop of Henle

198
Q

Where is antidiuretic hormone made?

Where does it go to next?

How is it released?

A

Produced in hypothalamus

Posterior pituitary gland

Stored in granules and released by exocytosis

199
Q

What are the 2 main functions of ADH?

A

To reduce water excretion

Stimulate vasoconstriction

200
Q

What 2 things stimulate the release of ADH?

Explain the pathophysiology

A

Raised plasma osmolarity (main)
- increased ADH reduces water excretion, diluting plasma to normal levels

Hypovolaemia/low blood pressure
- triggers release of angiotensin II

201
Q

Outline the release of ADH in the hypothalamus

A

Osmoreceptors shrink or swell according to plasma osmolarity

Increased plasma osmolarity will make water move out of osmoreceptors, making the cell shrink

Cell shrinkage causes the cell to release ADH

202
Q

Which receptor does ADH bind to on the collecting duct cell?

203
Q

Outline the action of ADH on the collecting duct cell

A

ADH - V2 receptor

Activates ATP –> cAMP —> protein kinase —-> protein phosphorylation —-> release of water channels from storage vesicles into cell membrane

Aquaporin-2

204
Q

Outline the formation of dilute urine

A

Ascending loop of Henle, pumps push solutes into the blood and leave water behind, making a dilute urine

In the absence of ADH, the urine will remain dilute because there is no water being reabsorbed

205
Q

Outline the formation of concentrated urine

A

Distal and collecting ducts are permeable to water IN THE PRESENCE OF ADH

Water moves so there is osmotic equilibrium with surrounding interstitium

ADH inserts aquaporin channels so water is moved out of the collecting duct

206
Q

What solutes drive the movement of water out of the collecting duct?

What systems help control this?

A

Urea (& NaCl) in the interstitium

Urea recirculation, Loop of Henle and Vasa Recta are important in maintaining this gradient

207
Q

By which mechanism is the medullary interstitium concentrated?

A

Counter current multiplier mechanism

208
Q

What 4 things are needed in a counter current multiplier mechanism?

A

Hairpin arrangement (LoH)

Fluid travelling in opposite directions

Different water permeabilities of the limbs

Ability of Na/K/2Cl transporter to ACTIVELY TRANSPORT solutes against a concentration gradient

209
Q

What is the result of a counter current multiplier mechanism?

A

Dilute filtrate entering distal nephron - water can move out by osmosis

Generates large increase in NaCl in medulla - creates an osmotic gradient

210
Q

The interstitial osmolarity is always the same as that in the….

A

Descending loop

211
Q

The difference in osmolarities in the descending and ascending limbs at any transverse level is only…

A

200 mOsmol

212
Q

Describe the vasa recta blood vessels and the counter current exchange

A

Hairpin arrangement allows nutrients to be delivered and water removed while minimising disruption to the medullary concentration gradient

213
Q

What are the two main clinical conditions of water regulation?

A

Too much ADH
- syndrome of inappropriate ADH (SIADH)

Too little antidiuretic hormone
- diabetes insipidus

214
Q

What are the causes, effects, and treatment of SIADH (too much ADH)?

A

Causes

  • pneumonia
  • small-cell lung carcinoma
  • drugs
  • meningitis

Effects

  • inappropriate water reabsorption
  • low plasma osmolality
  • low serum Na
  • urine inappropriately concentrated and high in Na

Treatment

  • identify and treat cause
  • restrict fluid intake
  • drugs that inhibit ADH effects (V2 antagonists)
  • avoid saline infusions
215
Q

What are the causes, effects, and investigations for diabetes insipidus (too little ADH)?

A

Inability to reabsorb water from distal nephron due to inadequate production (cranial DI) of insensitivity (nephrogenic DI) to ADH

Causes
Cranial DI - failure to produce/secrete ADH
- head trauma, neurosurgery, tumours, infection

Nephrogenic DI

  • drugs
  • electrolyte abnormalities
Effects
Polyuria
Thirst and polydipsia
Dilute urine
High plasma osmolality and serum Na

Investigations
Water/fluid deprivation tests

216
Q

Discuss fluid deprivation test

A

Water deprivation for 10 hours

Normal person, urine osmolarity will increase due to dehydration

Someone with diabetes insipidus (too little ADH), urine osmolarity will stay the same, because there is no ADH to reabsorb water in response to dehydration

Administration of synthetic ADH determines cranial or nephrogenic cause of DI

Cranial cause, administering ADH will increase urine osmolarity as water will be reabsorbed

Nephrogenic cause, urine osmolarity will stay the same as kidney can’t respond to ADH

217
Q

Describe how glucose and amino acids are reabsorbed in the proximal convoluted tubule

A

Glucose and Na+ taken up by SGLT2 - moves glucose against concentration gradient

Secondary active transport moves amino acids and Na+ into tubular cell

Glucose moves out via GLUT (facilitated diffusion)

Amino acids similar process

218
Q

Discuss glucose and transport maximum

A

Finite number of SGLT transporters on proximal tubule cells

If glucose in filtrate increases, transport maximum is reached where reabsorption can’t go any faster

Loss of glucose in urine

Pulls water with it

219
Q

Outline the regulation of acid base in the tubular lumen

A

Na+ reabsorption linked with H+ secretion Na+/H+ exchanger (NHE)

Removes hydrogen

Important for bicarbonate reabsorption

220
Q

Describe the process of reabsorption of solutes in the thick ascending limb

A

Na+K+2Cl- co-transporter

Positive charge in tubular lumen encourages paracellular reabsorption of cations (Ca2+, Mg2+)

Water can not be reabsorbed in thick ascending limb: produces a dilute urine

221
Q

What type of transporter is found in the early distal tubule?

A

Na+Cl- co-transporter

Further dilutes urine

Water is not reabsorbed here

222
Q

What are the 2 main cell types in the late distal and collecting tubule?

What is their functions?

A

Principle cells

  • sodium reabsorption
  • potassium secretion

Intercalated cells

  • potassium reabsorption
  • hydrogen secretion
223
Q

Describe the action of aldosterone on principal cells in the late distal tubule

A

Epithelial sodium channels allow sodium into cells (ENaC)

Number of ENaC and activity of Na/KATPase on blood side of cells is under the control of aldosterone

224
Q

What is the site of action and effects of aldosterone?

A

Collecting tubule and duct

Increased NaCl and H2O reabsorption
Increased K+ secretion

225
Q

What is the site of action and effects of ADH?

A

Distal tubule and collecting duct

Increased H2O reabsorption

226
Q

What is the site of action and effects of parathyroid hormone?

A

Proximal tubule, thick ascending loop of Henle

Decreased phosphate reabsorption
Increased Ca2+ reabsorption

227
Q

Which cells secrete the enzyme renin?

What triggers the release of renin?

A

Granular cells in the juxtaglomerular apparatus of the early distal tubule

Low afferent arteriole BP

Activation of sympathetic nerves that supply JGA

Low NaCl in distal tubule

228
Q

Draw out the RAAS system

A

Slide 29 of tubular processing lecture

229
Q

List 4 things that shifts potassium into cells

A

Insulin - emergency hyperkalaemia

Aldosterone - increases activity of Na/K ATPase on principle cells in distal convoluted tubule

Alkalosis - ?due to exchange of intracellular H+ for extracellular K+

B-adrenergic stimulation

230
Q

List 7 things that shifts potassium out of cells

A

Insulin deficiency

Aldosterone deficiency

B-adrenergic blockade

Acidosis - reduces Na/K ATPase activity, ? exchange of K+ for H+

Cell lysis

Strenuous exercise

Increased extracellular fluid osmolarity

231
Q

What 3 factors determine the rate of K+ excretion in the principle cells of the distal convoluted tubule?

A

Activity of Na+/K+ ATPase

K+ gradient between blood, principle cell and lumen

Permeability of luminal membrane to K+

232
Q

What 4 things regulate potassium excretion?

Do they increase or decrease the rate of potassium excretion and secretion?

A

Plasma potassium concentration
- increased K+ secretion

Aldosterone
- increased K+ secretion

Tubular flow rate
- increased K+ secretion

H+ concentration
- decreased K+ secretion

233
Q

How is aldosterone and increased tubular flow rate linked to potassium secretion?

A

Aldosterone leads to an increased rate of potassium excretion - it is controlled by plasma potassium

Increased tubular flow rate can occur with volume expansion, high Na or diuretics

This is useful because it allows independent potassium excretion even when aldosterone is suppressed by high sodium levels

234
Q

Give some signs and symptoms and causes of hypokalaemia

A

Asymptomatic
Muscle weakness
Cardiac arrhythmias

Reduced intake
Diuretics, diarrhoea, aldosterone excess

Address underlying cause
K+ supplementation

235
Q

Give some signs, symptoms and causes of hyperkalaemia

A

Excessive intake
Inadequate losses
Aldosterone deficiency
Acidosis

Cardiac arrythmias - tented T waves

Restrict intake
Calcium gluconate (stabalise myocardium)
Insulin and glucose (K+ into cells)
Aid excretion - fluids
236
Q

Reasons for problems with medications in patients with impaired renal function (4)

How can these problems be avoided/minimised?

A

Reduced renal excretion of a drug or its metabolites

Many side-effects poorly tolerated by patients in renal failure (e.g. increased potassium)

Increased sensitivity to some drugs

Some drugs less effective when renal function is reduced (e.g. diuretics)

Avoided/minimised by:
Reducing dose/frequency
Considering alternate drugs

237
Q

How does urine pH influence speed of drug excretion?

A

Most drugs are weak acids or bases:
In alkaline urine, acidic drugs are more readily ionised

In acidic urine, alkaline drugs are more readily ionised

238
Q

What are the 5 classes of diuretics?

A

Loop diuretics

Thiazides (+related) diuretics

Potassium sparing diuretics

Carbonic anhydrase inhibitors

Osmotic diuretics

239
Q

Define AKI

A

A significant deterioration in renal function, which is potentially reversible, over a period of hours or days.

240
Q

Give some causes of pre-renal failure

A

Renal hypoperfusion

  • systemic hypotension (bleeding, dehydration)
  • sepsis
  • renal artery stenosis
  • drugs (ACEi, NSAIDs)
241
Q

Give some causes of intrinsic renal failure

A

Primary renal disease
- glomerulonephritis

Secondary renal disease
- diabetes, SLE

Interstitial nephritis
- drugs

Secondary acute tubular necrosis
- after pre-renal failure

242
Q

Give some causes of post-renal failure

A

Obstruction/blockage of drainage from kidneys

243
Q

List some ECG changes seen in hyperkalaemia

A

Tented T waves

Prolonged QRS

Prolonged P-R interval

Loss of P waves

VF/asystole

244
Q

Which 2 tests are used in CKD classification?

A

GFR

Albuminuria

245
Q

List some complications of CKD

A

CVD

HTN

Anaemia

Bone-mineral metabolism

Poor nutrition/functional status

Progression of CKD

AKI

246
Q

What risk factors are associated with CKD progression?

A

HTN

DM

Albuminuria

CVD

Smoking

Ethnicity

NSAIDs

247
Q

List the 4 types of renal replacement therapy

A

Haemodialysis

Peritoneal dialysis

Transplatation

Conservative care

Block 1 (13 decks)

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