Anatomy and Physiology of the Kidney Flashcards
(247 cards)
1
Q
What are the three main processes performed by the nephron?
A
Filtration
Reabsorption
Secretion
2
Q
What makes up the renal corpuscle?
A
Bowman’s capsule
Glomerulus capillaries
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
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
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.
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
7
Q
What two parts make up the uriniferous tubule?
A
Nephron
Collecting duct
8
Q
Name the four parts of the nephron.
A
Renal corpuscle
Proximal tubule
Loop of Henle
Distal tubule
9
Q
Describe the blood supply of the kidney
A
Renal artery –> segmental artery –> interlobar arteries –> arcuate arteries –> interlobular arteries –> afferent and efferent arterioles
10
Q
What is the main extracellular fluid cation and anion?
A
Cation - sodium
Anion - chloride
11
Q
What is the main intracellular cation and anion?
A
Cation - potassium
Anion - phosphate
12
Q
What are the five human tissue types?
A
Epithelia, muscle, connective tissue, blood, nervous tissue
13
Q
What makes up the uriniferous tubule?
A
Nephron and collecting duct
14
Q
What is the name of the capillaries around the nephron (low pressure)?
A
Peritubular capillaries - for reabsorption and secretion
15
Q
What are the capillaries in Bowman’s capsule called?
A
Glomerular capillaries - high pressure for filtration
16
Q
What makes up the renal corpuscle? (2)
A
Glomerulus
Bowman’s Capsule
17
Q
Name the capillaries in the medulla around the Loop of Henle?
A
Vasa recta
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
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)
20
Q
Name the layers of the glomerular filtration barrier (3)
A
Glomerular capillary endothelium (fenestrated)
Basement membrane (negative charge)
Epithelium (podocytes)
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
22
Q
What two things are excluded from filtrate?
A
Blood cells
Plasma proteins
23
Q
Where does the majority of water, sodium, chloride, amino acid, and glucose reabsorption take place?
A
Proximal tubule
24
Q
Name the functions of the proximal tubule
A
Reabsorb - water, sodium, chloride, amino acids, glucose.
Secrete - drugs and waste molecules
25
What type of cells are found in the proximal tubule?
Simple cuboidal cells with microvilli (brush border to increase surface area).
Cuboidal cells have larger intracellular space - room for mitochondria to make transport proteins
26
Is the thin descending limb permeable or impermeable to water?
Permeable
27
What type of epithelium does the thin descending limb have?
Simple squamous epithelium
28
Is the thin ascending limb permeable or impermeable to water?
Impermeable
29
What type of epithelium does the thin ascending limb have?
Simple squamous epithelium
30
Do active or passive movements take place in the thin descending and ascending limbs?
Passive
31
Is the thick ascending limb permeable or impermeable to water?
Impermeable
32
What type of epithelial cell does the thick ascending limb have?
Simple cuboidal
33
What takes place in the thick ascending limb?
Active reabsorption of sodium and other solutes
34
What type of epithelial cells are found in the distal tubule?
Simple cuboidal
35
Is the distal tubule permeable or impermeable to water?
Variable depending on the presence of ADH
36
What forms the juxtaglomerular apparatus?
Macula densa
Extraglomerular mesangial cells (Lacis cells)
Granualar/Juxtaglomerular cells in afferent arteriole
37
Name the specialist cells in the early distal tubule at the JGA
Macula densa
38
What solutes does the macula densa detect?
Sodium
Chloride
39
Is the collecting duct permeable or impermeable to water?
Variable depending on the presence of ADH
40
What type of cells are found in the collecting duct?
Simple columnar
41
Define osmosis
The passive transport of water across a semipermeable membrane down a concentration gradient
42
What is the main osmotically active electrolyte in extracellular fluid?
Sodium
43
What is the main osmotically active electrolyte in intercellular fluid?
Potassium
44
What hormone is produced in the kidney in a hypoxic state?
What does it do?
Erythropoietin
Stimulates production of RBC precursors in bone marrow
45
Which enzyme is produced in the kidney to convert the inactive precursor of vitD to its active form?
1a-hydroxylase
46
How do you formulate the urinary excretion rate?
Filtration rate + secretion rate - reabsorption rate
47
What is glomerular filtration rate?
The volume of filtrate formed by all the nephrons in both kidneys per unit time.
48
What is the equation for GFR
GFR = Kf x NFP
Kf = glomerular capillary filtration coefficient
NFP = net filtration pressure
49
What determines the glomerular capillary filtration coefficient (Kf)
Surface area for filtration (how many nephrons available)
Hydraulic conductivity (permeability) of the filtration barrier (3 layers of renal corpuscle)
50
What increases eGFR?
| arterioles
AA dilation and/or EA constriction
51
What decreases eGFR?
| arterioles
AA constriction and/or EA dilation
52
Name 3 substances that have an affect on glomerular pressure
Angiotensin II - constricts EA
Prostaglandins - vasodilate AA
Noradrenaline - vasoconstrict AA
53
Why do peritubular capillaries favour reabsorption?
High oncotic pressure (concentrated plasma proteins) and low capillary hydrostatic pressure (fluid on vessel walls)
54
What are the two mechanisms of autoregulation of eGFR?
Myogenic response
Tubuloglomerular feedback
55
At which vertebral level is the hilum of the kidney?
L1
56
Which vertebral levels does the kidney normally sit between?
T11 - L2/3
57
Which paracrine factor is released in HTN in the tubuloglomerular feedback system?
What does this cause?
Adenosine
Constriction of AA smooth muscle
58
Which endocrine factor is released in hypotension in the Tubuloglomerular feedback system?
Which cells is it released from?
What does it cause?
Renin
Gramilin cells
Constriction of EA muscle
59
What does low quantities of sodium chloride in the macula densa cause?
Secretion of renin.
Afferent arteriole dilation
60
What type of epithelium is found on the lining of the bladder?
Transitional epithelium
61
Which nerve supplies the urinary sphincters?
Pudendal nerve S2-4
62
Describe the type of muscle in the urinary sphincters
Internal sphincters - smooth muscle (involuntary)
| External sphincters - skeletal muscle (voluntary)
63
Where do sensory nerves from the superior part of the bladder (on the peritoneum) travel to?
T12-L2
| Travel to CNS with sympathetic nerves
64
Where do sensory nerves inferior to the peritoneum travel to?
S2-4
| Travel to CNS with parasympathetic nerves
65
How do NSAIDs reduce eGFR?
Inhibit prostaglandin production - AA become constricted - reduces eGFR
66
How do ACEi/ARB reduce eGFR?
Prevent production/action of angiotensin II - EA become dilated - reduces eGFR
67
Where do carbonic anhydrase inhibitors have their site of action?
Proximal tubule
68
Where do osmotic diuretics have their site of action?
Proximal tubule and descending loop of Henle
69
Where do loop diuretics have their site of action?
Ascending loop of Henle
70
Where do thiazides have their site of action?
Early distal tubule
71
Where do potassium sparing diuretics have their site of action?
Late distal tubule and collecting duct.
72
Name the five classes of diuretics
```
Potassium sparing diuretics
Osmotic diuretics
Loop diuretics
Carbonic anhydrase inhibitors
Thiazide diuretics
```
73
How do loop diuretics cause hypokalaemia?
Increased delivery of Na+ to distal tubule --> increased uptake of Na+ in distal tubule --> secretion of K+.
74
How to carbonic anhydrase inhibitors lead to metabolic acidosis?
Prevents absorption of HCO3- into blood --> less alkaline in blood --> more acidic environment in blood.
Prevents secretion of H+ molecules --> more intra/extracellular.
75
Describe the location of the uriniferous tubule in relation to the cortex and medulla of the kidney
Cortex - mainly renal corpuscles, proximal tubule, distal tubule
Medulla - mostly LoH and collecting ducts
76
What factor determines if a nephron is cortical or juxtamedullary?
The position of the renal corpuscle
77
Where can arcuate arteries be found?
Running along the corticomedullary junction
78
Name the 2 capillary beds that blood passes through in the kidney
Glomerular capillaries
- high pressure
- filtration
Peritubular capillaries
- low pressure
- reabsorption/secretion
79
What type of cells provide support between the glomerular capillary loops?
Mesangial cells
80
What 5 things are reabsorbed in the PCT?
Sodium
Water
Chloride
Amino acids
Glucose
81
What is the net result of filtrate passing through the loop of Henle?
Produce concentrated urine
Hyperosmolar interstitium in medulla
82
What surrounds the collecting duct of a nephron?
What is the key role of the collecting duct?
Medullary interstitium with a high concentration of solutes
Produces a concentration gradient
Key role in regulating degree of urine concentration
83
In a typical male, what % of body weight is water?
60%
| 42 litres
84
42 litres total in a typical male, how much is intracellular and extracellular?
Intracellular - 28 litres
Extracellular - 14 litres
85
What are the 2 main compartments of extracellular fluid (ECF)?
Interstitial fluid - surrounds the cells
Plasma - non-cellular component of blood
86
What separates intracellular and extracellular fluid?
Semipermeable membranes
87
What is the main difference between plasma and interstitial fluid?
Plasma has proteins in it
Capillary membrane is highly permeable to water and electrolytes but not to most plasma proteins
88
What type of anaemia can be seen in kidney disease?
Explain the pathophysiology
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
89
What 5 factors can decrease tissue oxygenation?
Low blood volume
Anemia
Low Hb
Poor blood flow
Pulmonary disease
90
Which 2 muscles are posterior relations of the kidney?
Psoas major
Quadratus lumborum
91
Is the kidney inter or retro peritoneal?
Retroperitoneal
92
What is Morrison's pouch?
Space between liver and R kidney.
Potential space for infection to spread into when lying down (gravity dependent)
93
What space communicates across the midline between both kidneys, and therefore is a potential route of infection spread?
Renal fascia space
94
From closest to furthest, which 3 fats/fascia surround the kidney?
Perinephric fat
surrounded by Renal Fascia
Paranephric fat
surrounded by Psoas Fascia
95
What does the kidney develop from in utero?
Metanephros (intermediate mesoderm)
Ureteric bud
96
Describe the formation of the blood supply to the kidney
Kidneys start at lower vertebral level, have to ascend
Gets new blood supply as it ascends
Can cause problems
97
What is a polar renal artery?
Kidney with 2 arteries
1 is a remnant of kidney being at a lower vertebral level
98
What is an aberrant renal artery?
A second renal artery that blocks the ureter
Can cause decreased renal function
99
What is a horseshoe kidney?
What problem can it cause?
Joining of the inferior poles of both kidneys
Joins under the IMA - potential site of restricted blood flow
100
What is the difference between a bifid and duplicate ureter?
Bifid - 2 ureteric openings at the kidney, join together before reaching the bladder
Duplicate - 2 ureters and 2 openings to the bladder
101
What does the bladder develop from in utero?
Anterior part of cloaca with allantois attached
102
What is the purpose of the allantois in utero?
Formation of blood cells
103
List 3 problems that the allantois can cause in adults
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
Describe the arterial blood supply to the right kidney
The right renal artery is longer, and crosses the vena cava posteriorly
105
Do the renal arteries arise above or below the SMA?
Immediately below
106
Which other vein joins the L renal vein?
Left testicular/ovarian veins
Only on the L side
The R testicular/ovarian veins drain directly into the IVC
107
Describe the referred pain pattern of a renal calculus
Shifting 'loin-groin' pain
108
How do visceral sensory nerves from the ureters travel to the CNS?
Alongside sympathetic nerves
109
Where are the 3 common places for a renal stone to get stuck?
Pelvic-ureteric junction (PUJ)
Where the ureter crosses the iliac vessels
Vesico-ureteric junction (VUJ)
110
What is the major differential/concern for an elderly patient presenting with presumed left sided renal colic?
Ruptured AAA
111
Where do the ureters enter the bladder?
At the level of the ischial spines
Vesico-ureteric junction
112
What cell type lines the bladder?
Transitional epithelium (urothelium)
113
Where is the trigone of the bladder?
Bladder wall between the 2 ureters and urethra
114
What prevents urine reflux during micturition?
Vesico-ureteric valve (thickening of detrusor muscle)
115
List the 3 male sphincters
Internal urethral sphincter
External urethral sphincter
Compressor urethrae
116
List the ?4 female sphincters
Internal urethral sphincter
External urethral sphincter
Compressor urethrae
Sphincter urethrovaginalis
117
Which nerve are most urinary sphincters innervated by?
Pudendal nerve S2-4
118
Are the internal and external urethral sphincters smooth or skeletal muscle?
Internal urethral sphincter
- smooth muscle
- involuntary
External urethral sphincter
- skeletal muscle
- voluntary
119
What is the source of the bladder's blood supply?
Internal iliac artery
120
What tissue layers does a suprapubic catheter pass through to get to the bladder?
Skin
Subcutaneous tissue,
Superficial fascia
Linea alba (midline, remember we are below umbilicus)
Tranversalis fascia
Parietal peritoneum
Bladder wall
121
Which 2 ligaments support the bladder in females?
Pubo-vesical ligament
Levator ani
122
Which 2 ligaments support the bladder in males?
Levator ani
Pubo-prostatic ligament
123
What is a cystocele?
Protruding bladder caused by weakness of bladder support in females
124
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?
T12-L2
Top of the bladder is covered in peritoneum
Gets back to the CNS with sympathetic nerves
125
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?
S2-4
Bladder is retorperitoneal
Gets back to CNS with parasympathetic nerves
126
What is the pelvic pain line?
An organ in the pelvis is said to be "above the pelvic pain line" if it is in contact with the peritoneum
127
What nerves allow us to pee?
What do they do?
Parasympathetic nerves S2-4
Contract detrusor muscle
Relax internal urethral sphncter
128
What nerve tell us to stop peeing?
What do they do?
Sympathetic L1-2
Constricts internal urethral sphincter
Relaxes detrusor muscle
129
What role do somatic nerves splay on micturition?
Tell us to stop peeing
Pudendal nerve (S2-4)
Contracts external urethral sphincter
130
List the 3 categories of lower urinary tract symptoms (LUTS)
Give some examples in each
Storage LUTS
Voiding LUTS
Post-micturition LUTS
131
Give some examples of storage LUTS
Incontinence
Urgency
Frequency
Nocturia
132
Give some examples of voiding LUTS
Poor stream
Hesitancy
Dysuria
Double voiding
Retention
133
Give an example of post-micturition LUTS
Terminal dribbling
134
Define urinary incontinence
Involuntary loss of urine in sufficient amount or frequency to constitute a social and/or health problem
135
Give 6 types of incontinence
Stress
Urge
Overflow
Functional
Continuous
Childhood
136
Describe stress incontinence
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
Describe urge incontinence
Involuntary urine leakage accompanied/preceded by urgency
Overactive bladder
Commonest cause of incontinence >50
138
Describe overflow incontinence
Prolonged problems with bladder emptying lead to chronic retention and detrusor failure
Most often men
139
Describe functional incontinence
Consequence of something not involving the urinary tract
- mobility
- dementia
- diuretics
140
Describe urodynamics
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
Describe outflow cystometry
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
What drugs can be given for urge incontinence/overactive bladder?
Describe their MoA
Give side effects
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
What drugs can be given for urinary retention and BPH?
Describe their MoA
Give side effects
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
What can cause urinary retention?
BPH
Prostate CA
Prostatitis
Haematuria
Tumours
Stones
145
Describe BPH
Give symptoms
Enlarged prostate blocking urethra
```
SYMPTOMS
Hesitancy
Straining
Weak flow
Stop-start
Nocturia
Incontinence
Feeling of incomplete emptying
```
146
Describe the international prostate symptom score
7 symptom questions
- frequency
- nocturia
- urgency
- hesitancy
- poor stream
- intermittency
- incomplete emptying
1 QoL question
147
What examinations/investigations would you do for BPH?
Prostate symptom score
PSA
Abdo exam
DRE
Transrectal USS
148
What drug would you give in BPH management?
Doxazosin
| selective a-1 blocker
149
In which zone of the prostate do most cancers start?
Peripheral zone (outer zone furthest away from urethra)
150
Which zone of the prostate gets bigger with age and is usually responsible for BPH?
Transition zone (surrounds the urethra)
151
Describe the process of renal stone formation
Crystalline growth
Has to be stasis of urine for calcium oxalate crystal to aggregate
152
Describe struvite stones
What causes them?
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
Describe uric acid stones
Accumulation of urate from purine metabolism
154
Describe a typical presentation of renal colic
Loin to groin pain
Haematuria
Vomiting
Irritative voiding symptoms
155
Urinary excretion rate =
Filtration rate + secretion rate - reabsorption rate
156
What is the net filtration pressure?
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
What is the equation for net filtration pressure (NFP)?
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
If someone has urinary tract obstruction, which part of the net filtration formula will be affected?
Pb - bowman's capsule hydrostatic pressure
159
What determines glomerular hydrostatic pressure (Pg)?
BP
Afferent arteriole resistance
Efferent arteriole resistance
160
Why is Pg the most important pressure in maintain GFR?
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
What does angiotensin II do to net filtration pressure?
Preferentially constricts efferent arteriole
Increases Pg (glomerular hydrostatic pressure)
162
What do prostaglandins and atrial natriuretic peptide (ANP) do to net filtration pressure?
Vasodilate afferent arteriole
Increases Pg (glomerular hydrostatic pressure)
163
What do NA, adenosine and endothelin do to net filtration pressure?
Vasoconstrict afferent arteriole
Reduces Pg (glomerular hydrostatic pressure)
164
Why do peritubular capillaries favour reabsorption?
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
What are the 2 mechanisms of autoregulation of GFR
Myogenic response
Tubuloglomerular feedback
166
Define a myogenic response
Inherent ability of smooth muscle in afferent arterioles to respond to changes in vessel circumference by contracting or relaxing
167
Outline the myogenic autoregulation response in the kidney
```
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
Outline the tubuloglomerular feedback system in the kidney
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
Which cells detect changs in NaCl?
Where are they found?
Macula densa cells
Early part of the dista tubule
170
Describe the tubuloglomerular feedback in the kidney in increased BP
```
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
Describe the tubuloglomerular feedback in the kidney in reduced BP
```
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
What does proteinuria/albuminuria indicate damage to?
Filtratation barrier
Strong association between proteinuria and rate of disease progression in CKD
173
Define renal clearance
The volume of plasma from which a substance is completely cleared by the kidneys per unit time
174
What is the equation for renal clearance?
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
Which substance is filtered, not reabsorbed or secreted and is egual to GFR?
Inulin
176
How is urea handled by the kidney?
How does this reflect GFR?
Filtered, partially reabsorbed
Less than GFR
177
How is creatanine handled by the kidney?
How does this reflect GFR?
Filtered and secreted
Greater than GFR
178
How is creatanine made?
What can affect creatinine?
Formed from the breakdown of creatine, skeletal muscle component
```
Age
Sex
Muscle mass
Diet
Ethnicity
Malnutrition
```
179
Why is creatinine clearance not a suitable measure of renal function/GFR?
Requires 24hr urine collection - compliance, time, reliability
Small amount of secretion of creatinine means GFR tends to be overestimated
180
Which 3 tests are routinely used to assess renal function?
Serum urea
Serum creatinine
eGFR
Single blood test
181
What is urea?
What happens to it in the kidney?
What can affect urea?
Nitrogen containing metabolic waste product from the metabolism of proteins
Filtered, partially reabsorbed
Dehydration will mean more urea is reabsorbed
182
List 4 things that can increase urea production
High protein diet
Increased catabolism (trauma, cancer)
GI bleed
Drugs (corticosteroids, tetracyclines)
183
List 2 things that reduce urea elimination
Renal disease that causes a reduction in GFR
Poor renal blood flow (hypotension, dehydration)
184
When analysing serum urea, what does it need to be compared to?
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
Why is creatinine not a useful tool to detect renal function on its own?
You can lose ~50% of renal function (GFR) and yet still appear to have a serum creatinine that lies within the ‘normal’ range
186
What factors determine eGFR?
Serum creatinine
Age
Sex
Ethnicity
187
Give some signs and symptoms of hypovolaemia
Symptoms
- thirst
- dizziness on standing
- confusion
Signs
- low JVP
- weight loss
- dry mucous membranes
- reduced skin turgor
- reduced urine output
188
Give some signs and symptoms of hypervolaemia
Symptoms
- ankle swelling
- breathlessness
Signs
- raised JVP
- oedema
- weight gain
- hypertension
189
What is the minimum obligatory urine production per day to excrete waste solutes?
500mls day
190
Why can we alter water excretion independently of solute excretion?
If you drink large volumes of water, the amount of solutes excreted remains unchanged
This allows plasma osmolarity to remain constant
191
If someone drinks a lot of water, will the osmolarity of urine be more or less than plasma?
Osmolarity will be less - more water is excreted compared to solutes
Can excrete water independently of solutes
192
What is the formula for urine osmolarity?
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
What is the maximum concentration of urine?
1200 mOsm/L
Therefore, typical obligatory urine volume = 0.5L / day
194
What can cause increased water excretion?
Polyuria
Excessive water ingestion
Inability to concentrate urine (tubular damage, diabetes insipidus)
195
What can cause increased solute excretion?
Polyuria
Diuretics (or failure to reabsorb sodium)
Glycosuria (diabetes)
196
What can cause decreased water/solute excretion?
Dehydration
Low extracellular volume
Poor renal perfusion
197
What does water reabsorption in the collecting ducts require?
Insertion of water channels (aquaporins) regulated by ADH
An osmotic gradient generated by the countercurrent system in the loop of Henle
198
Where is antidiuretic hormone made?
Where does it go to next?
How is it released?
Produced in hypothalamus
Posterior pituitary gland
Stored in granules and released by exocytosis
199
What are the 2 main functions of ADH?
To reduce water excretion
Stimulate vasoconstriction
200
What 2 things stimulate the release of ADH?
Explain the pathophysiology
Raised plasma osmolarity (main)
- increased ADH reduces water excretion, diluting plasma to normal levels
Hypovolaemia/low blood pressure
- triggers release of angiotensin II
201
Outline the release of ADH in the hypothalamus
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
Which receptor does ADH bind to on the collecting duct cell?
V2
203
Outline the action of ADH on the collecting duct cell
ADH - V2 receptor
Activates ATP --> cAMP ---> protein kinase ----> protein phosphorylation ----> release of water channels from storage vesicles into cell membrane
Aquaporin-2
204
Outline the formation of dilute urine
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
Outline the formation of concentrated urine
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
What solutes drive the movement of water out of the collecting duct?
What systems help control this?
Urea (& NaCl) in the interstitium
Urea recirculation, Loop of Henle and Vasa Recta are important in maintaining this gradient
207
By which mechanism is the medullary interstitium concentrated?
Counter current multiplier mechanism
208
What 4 things are needed in a counter current multiplier mechanism?
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
What is the result of a counter current multiplier mechanism?
Dilute filtrate entering distal nephron - water can move out by osmosis
Generates large increase in NaCl in medulla - creates an osmotic gradient
210
The interstitial osmolarity is always the same as that in the....
Descending loop
211
The difference in osmolarities in the descending and ascending limbs at any transverse level is only...
200 mOsmol
212
Describe the vasa recta blood vessels and the counter current exchange
Hairpin arrangement allows nutrients to be delivered and water removed while minimising disruption to the medullary concentration gradient
213
What are the two main clinical conditions of water regulation?
Too much ADH
- syndrome of inappropriate ADH (SIADH)
Too little antidiuretic hormone
- diabetes insipidus
214
What are the causes, effects, and treatment of SIADH (too much ADH)?
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
What are the causes, effects, and investigations for diabetes insipidus (too little ADH)?
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
Discuss fluid deprivation test
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
Describe how glucose and amino acids are reabsorbed in the proximal convoluted tubule
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
Discuss glucose and transport maximum
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
Outline the regulation of acid base in the tubular lumen
Na+ reabsorption linked with H+ secretion Na+/H+ exchanger (NHE)
Removes hydrogen
Important for bicarbonate reabsorption
220
Describe the process of reabsorption of solutes in the thick ascending limb
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
What type of transporter is found in the early distal tubule?
Na+Cl- co-transporter
Further dilutes urine
Water is not reabsorbed here
222
What are the 2 main cell types in the late distal and collecting tubule?
What is their functions?
Principle cells
- sodium reabsorption
- potassium secretion
Intercalated cells
- potassium reabsorption
- hydrogen secretion
223
Describe the action of aldosterone on principal cells in the late distal tubule
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
What is the site of action and effects of aldosterone?
Collecting tubule and duct
Increased NaCl and H2O reabsorption
Increased K+ secretion
225
What is the site of action and effects of ADH?
Distal tubule and collecting duct
Increased H2O reabsorption
226
What is the site of action and effects of parathyroid hormone?
Proximal tubule, thick ascending loop of Henle
Decreased phosphate reabsorption
Increased Ca2+ reabsorption
227
Which cells secrete the enzyme renin?
What triggers the release of renin?
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
Draw out the RAAS system
Slide 29 of tubular processing lecture
229
List 4 things that shifts potassium into cells
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
List 7 things that shifts potassium out of cells
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
What 3 factors determine the rate of K+ excretion in the principle cells of the distal convoluted tubule?
Activity of Na+/K+ ATPase
K+ gradient between blood, principle cell and lumen
Permeability of luminal membrane to K+
232
What 4 things regulate potassium excretion?
Do they increase or decrease the rate of potassium excretion and secretion?
Plasma potassium concentration
- increased K+ secretion
Aldosterone
- increased K+ secretion
Tubular flow rate
- increased K+ secretion
H+ concentration
- decreased K+ secretion
233
How is aldosterone and increased tubular flow rate linked to potassium secretion?
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
Give some signs and symptoms and causes of hypokalaemia
Asymptomatic
Muscle weakness
Cardiac arrhythmias
Reduced intake
Diuretics, diarrhoea, aldosterone excess
Address underlying cause
K+ supplementation
235
Give some signs, symptoms and causes of hyperkalaemia
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
Reasons for problems with medications in patients with impaired renal function (4)
How can these problems be avoided/minimised?
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
How does urine pH influence speed of drug excretion?
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
What are the 5 classes of diuretics?
Loop diuretics
Thiazides (+related) diuretics
Potassium sparing diuretics
Carbonic anhydrase inhibitors
Osmotic diuretics
239
Define AKI
A significant deterioration in renal function, which is potentially reversible, over a period of hours or days.
240
Give some causes of pre-renal failure
Renal hypoperfusion
- systemic hypotension (bleeding, dehydration)
- sepsis
- renal artery stenosis
- drugs (ACEi, NSAIDs)
241
Give some causes of intrinsic renal failure
Primary renal disease
- glomerulonephritis
Secondary renal disease
- diabetes, SLE
Interstitial nephritis
- drugs
Secondary acute tubular necrosis
- after pre-renal failure
242
Give some causes of post-renal failure
Obstruction/blockage of drainage from kidneys
243
List some ECG changes seen in hyperkalaemia
Tented T waves
Prolonged QRS
Prolonged P-R interval
Loss of P waves
VF/asystole
244
Which 2 tests are used in CKD classification?
GFR
Albuminuria
245
List some complications of CKD
CVD
HTN
Anaemia
Bone-mineral metabolism
Poor nutrition/functional status
Progression of CKD
AKI
246
What risk factors are associated with CKD progression?
HTN
DM
Albuminuria
CVD
Smoking
Ethnicity
NSAIDs
247
List the 4 types of renal replacement therapy
Haemodialysis
Peritoneal dialysis
Transplatation
Conservative care
