MET2 Revision3 Flashcards
Explain what happens to serum Ca2+ levels during acidosis and alkalosis [2]
Acidosis: causes Ca2+ to increase
Alkolosis: causes Ca2+ to decrease
Ca2+ and H+ bind to same place on albumin: acidosis the H= competes with Ca2+ and causes more ionised Ca2+ in the blood
Explain the importance of Ca2+ in cardiac AP [1]
How does low
Calcium is involved in maintaining the plateau phase:
- Na in
- Ca out.
Extracellular Ca2+: blocks the voltage gated Na channels in the cardiac cell membrane.
Low Ca2+ levels: less blockade of VGNaCs = tachyarrhythmias
Parathyroid hormone (PTH) is secreted from which gland? [1]
Effect of PTH secretion? [3]
PTH from parathyroid
PTH causes: overall increase in Ca2+ serum levels by:
- Increased renal Ca2+ reabsorption.
- Increased bone Ca2+ release.
- Increased gut absorption via release of vitamin D (1,25vitD).
What inhibits the release of PTH? [1]
Ca2+ levels being too high (-ve feedback)
What is the effect of Ca2+ binding to Ca2+ sensing receptor on parathyroid? [3]
Ca2+ binds to Ca2+ sensing receptor on parathyroid. Causes:
* Reduces PTH secretion
* Increases breakdown of stored PTH in vesicles
* Suppresses transcription of PTH gene.
What is the activated form of vitamin D? [1]
1α,25-dihydroxyvitamin D
What effect does the inactivaton of CaSR have? [1]
What effect does the overactivation of CaSR have? [1]
What effect does the inactivaton of CaSR on parathyroid gland have? [1]
Hypercalcemia: no -ve feedback
What effect does the overactivation of CaSR on parathyroid gland have? [1]
Hypocalcaemia: too much -ve feedback
Why does PTH cause an increase in phosphate excretion?
Bone is broken down to release Ca2+, but also P is released
Therefore the kidney needs to excrete P to compensate
Effect of PTH on
a) Kidney [2]
b) Bone [2]
c) Intestine [2]
Effect of PTH on
a) Kidney: decreases Ca2+ excretion AND increases P excretion (one is broken down to release Ca2+, but also P is released. Therefore the kidney needs to excrete P to compensate)
b) Bone: Increases Ca2+ and phosphate reabsorbtion
c) Intestine: Increases Ca2+ and phosphate
Which areas of nephron cause reabsorbtion of Ca2+ dependently / independently of PTH? [3]
PCT: independent
LoH: independent
DCT: PTH dependent
Explain how Ca2+ is reabsorbed at PCT [2]
At PCT:
- independent of PTH
- Driven by NaKCl2 channel causing a voltage gradient paracellularly which Ca2+ flows (coupled with Na+ reabsorbtion)
Explain how Ca2+ is reabsorbed at LoH [2]
Driven by voltage gradient: Para/transcellular
Coupled with Na+ reabsorbtion: NKCC2 channel
Why do thiazide diuretics raise serum calcium?
Increase Ca2+ reabsorbtion into the blood / raises Ca2+ serum levels:
- Blocks Na/Cl symporter on luminal side
- This drops the Na conc. In tubular cell
- This creates Na diffusion gradient
- Na diffusion increases from capillary into tubular
cell - across Na/Ca exchanger -> takes Na into cell and transports Ca2+ into blood. -> increase in blood Ca levels.
Effect of PTH on:
- NaPi transporters (and therefore P reabsorbtion)? [1]
- Vit. D activation? [1]
- PCT GNG? [1]
- Na/H20/HCO3- reabsorbtion? [1]
- Down-regulation of NaPi transporters: Reduced phosphate reabsorption
- Vitamin D Activation Stimulation of 25(OH) D3 –> 1,25(OH)2 D3 (inactivates 1,25-dihydroxyvitamin D)
- Proximal tubule gluconeogenesis
- Inhibits sodium/water/bicarbonate reabsorption via effects on Na/H exchanger and Na/K ATPase
What effect does PTH have on bone tissue? [2]
COME BACK
Where do you find vit. D receptors? [2]
Role of vit D? [2]
Receptors: nucleus and cytoplams
Role: Upregulates Ca2+ transporters
Effect of PTH on bone remodelling xx
The conversion of vit. D to WHAT is regulated? [1]
The conversion of vit. D to WHAT is unregulated? [1]
What are the enzymes used for each? [2]
Conversion of vit D to 25(OH)D in the liver is an unregulated process, under the action of p450 enzymes. The half life of 25(OH)D is 2-3 weeks.
The conversion of vit D to 1,25(OH)D is highly regulated, via 1αhydroxylase
Why would chronic infection (e.g from sarcoidosis / TB granuloma) cause hypercalcemia?
- Macrophages produce vitamin D
- Release of vitamin D is converted to 1 25 dihydroxyvitamin dby 1α hydroxylase
- Causes increase in serum calcium
The major role of calcitriol (1,25 (OH) D) is [2]?
The major role of calcitriol is in increasing gut calcium and phosphate absorption.
How does negative feedback of activation of vitamin D receptor work?
In most cells there is a negative feedback inhibition: activation of the VDR inhibits the action of 1α hydroxylase (which converts vit D to active form), therefore reducing the amount of activated vitamin D able to bind to the VDR.
other vit d effects
What does the hormone FGF23 do? [1]
Which cells are they secreted from? [1]
What does FGF23 do to 1-a-hydroxylase? [1]
What does the hormone FGF23 do? [1]
Reduces serum P levels USED FOR WHEN GET P EXCRETED FROM FROM BONE BUT NEED TO EXCRETE VIA RENAL SYSTEM
It inhibits renal tubular reabsorption of phosphate
Which cells are they secreted from? [1]
Secreted by osteocytes
What does FGF23 do to 1-a-hydroxylase? [1]
reduces 1-a-hydroxylase: less activated vit. D
FYI
Activating mutation in FGF23 - Autosomal dominant hypophosphataemic rickets
Tumour induced osteomalacia - paraneoplastic FGF23
Familial tumoral calcinosis - low levels FGF23
Explain 3 classes of symptoms seen in hypercalcemia
Hypercalcemia
Symptoms
Neuropsychiatric disorders: due to reduced membrane excitibility causing reduced nerve transmisison in the brain
GI abnormalities:
* Constipation / pancreatitis: reduced membrane excitibility causes less muscle contraction
Renal dysfunction:
* Nephrogenic Diabetes Insipidus: Ca2+ binds to CaSR in nephrone, which down regulates NaKCL2 symporter
Renal stones & Renal failure due to XS Ca2+ in urine
What is primary cause of hypercalcemia? [1]
Malignancy in parathyroid gland is main cause, usually from bone metastasis
How do you treat hypercalcemia?
Expand plasma volume IV saline: reduces voltage gradient in tubular cells -> less Ca ++ reabsorbed
Reduce Ca release from bone
Treat underlying cause
What are primary, secondary and tertiary causes of hyperparathyroidism?
Primary: Parathyroid adenoma/carcinoma/hyperplasia
Secondary: Physiological compensation for hypocalcemia or Vitamin D deficiency. Can create tertiary
Tertiary: Autonomous PTH production following chronic secondary.
What pathology can primary hyperparathyroidism lead to and why? [2]
hypercalcaemia + excess PTH -> osteoporosis.
(PTH) removes calcium from bones all patients with a parathyroid problem will eventually develop thin bones. Bones with osteoporosis due to parathyroid problems can ache and hurt because the PTH is actively destroying the bone. Bones with osteoporosis are fragile bones which are much more susceptible to fractures and breaks.
How can you ID if have primary Hyperparathyroidism? [4]
Neck USS
MIBI scan
CT scan
Parathyroid Venous Sampling
How do you treat hypoparathyroidism acutely and chronically? [2]
Acutely: give Ca2+
Chronically: Give activated vit D: increased gut absorb
How would a patient with hyperparathyroidism present? [4]
Neuromuscular Excitability:
Cardiac tachyarrhythmia
Tetany
Seizures
Psychiatric manifestations
What would be overall causes of Hypocalcemia? [3]
PTH problems
Vit D problems (e.g. nutritional deficiency)
Compartment shifts
kidney, [] converts 25-hydroxyvitamin-D into 1,25-dihydroxyvitamin-D
kidney, 1-α-hydroxylase converts 25-hydroxyvitamin-D into 1,25-dihydroxyvitamin-D
Label A-E
A: Renal artery
B: Segmental arteries
C: Interlobar arteries
D: Arcuate arteries
E: Interlobal arteries
Label A-D
A: Afferent arterioles
B: Glomerulus
C: Efferent arterioles
D: Peritubular capillaries / vasa recta
Where do you examine for tenderness for kidneys (name / vert level) [2]
Renal Angle [1]
Junction of 12th rib and lateral border of erector spinal [1]
What is the hepatorenal recess a potential space between? [2]
Potential space that separates the liver and the right kidney [2]
Hepatorenal recess can have fluid accumulate because of? [3]
haemoperitoneum (is the presence of blood in the peritoneal cavity) [1]
ascites [1]
pancreatitis [1]
Which structures lie adjacent to the anterior aspect of the right kidney:
Label
A
B
C
D
E
Which structures lie adjacent to the anterior aspect of the LEFT kidney
A
B
C
D
E
F
G
What are the 3 main nerves associated with the kidney? [3]
Iliohypogastric
Ilioinguinal
Genitofemoral
Which is the only nerve of the lumbar plexus that passes through the psoas major? [1]
Iliohypogastric
Ilioinguinal
Genitofemoral
Lateral femoral cutaneous nerve
Femoral nerve
Which is the only nerve of the lumbar plexus that passes through the psoas major? [1]
Iliohypogastric
Ilioinguinal
Genitofemoral
Lateral femoral cutaneous nerve
Femoral nerve
Label each colour
Purple: psoas major
Green: Quadratus lumborum m
Red: Transversus abdominis m.
Blue: diaphragm
Label A-C xx
A: perinephtic fat
B: renal fascia
C: paranephric fat
Para = alongside
Peri = surrounding or around
The renal fascia, commonly known as Gerota’s fascia, is a collagenous connective tissue sheath which separates the [] fat from the [] fascia
The renal fascia, commonly known as Gerota’s fascia, is a collagenous connective tissue sheath which separates the perirenal fat from the pararenal fascia
Label A-E
At which structure in the kidney is waste is drained into renal pelvis?
renal papilla
Which veins drain into the left renal vein? [3]
left gonadal (ovarian/testicular) vein,
left inferior phrenic vein
left adrenal veins.
What are the 3 layers of the ureter wall? [3]
Transitional epithelial mucosa
Smooth muscle muscularis
Fibrous connective tissue adventitia
How does urine reach the bladder?
Ureters actively propel urine to the bladder via response to smooth muscle stretch
Where are the 3 places that kidney stones get stuck in the ureters? [3]
Uteropelvic junction
Pelvic inlet (and iliac vessels)
Uterovesical junction
Ureter nerve supply:
Which nerves are nerve due to kidney stones referred along? [2]
Where is the pain common felt? [1]
Why does the referred pain change? [1]
The loin pain is referred along the ilioinguinal and the iliohypogastric nerves (L1)
As the stone descends the patient may start to feel pain descend over the groin and scrotum/labium majora (“from loin to groin”)
This is because of the changing nerve segments and the pain is now referred through the genitofemoral nerve (L1,2)
What is the muscle of the bladder called? :)
Muscle of the bladder: detrusor muscle
Different role of internal and external urethral sphincter in males? [2]
Internal urethral sphincter (males): involuntary sphincter at the bladder-urethra junction (preventing retrograde ejaculation)
External urethral sphincter: voluntary sphincter surrounding the urethra as it passes through the urogenital diaphragm
What is sympathetic innervation of bladder from? [1] What is the effect? [1]
What is parasympathetic innervation of bladder from? [1] What is the effect? [1]
What is somatic innervation of bladder from? [1] What is the effect? [1]
Sympathetic (hypogastric n; T12-L2)
Stimulate contraction (closure) of the internal urethral sphincter
Inhibit the detrusor muscle (prevents contraction and bladder emptying)
Parasympathetic (S2-S4)
Stimulate the detrusor muscle to contract
Inhibits (opens) the internal urethral sphincters
Somatic - external urethral sphincter (Pudendal n.S2-S4
Vit D —(1)—> X —(2)—> Y
Name 1, 2 and X and Y [4]
Vit D—> 25(OH)D (25-hydroxyvitamin D₃) —-> 1,25-dihydroxvitamin D(3)
1: P450 enyzmes (In the liver)
2: 1 alpha hydroxylase
Label the blue and green arrows [2]
Blue arrows: segmental arteries
Green arrows: interlobar arteries
Label the arteries
Where is a kidney stone in theis imaging?
Uteropelvic junction
Pelvic inlet
Uterovesical junction
Where is a kidney stone in theis imaging?
Uteropelvic junction
Pelvic inlet
Uterovesical junction
Where is a kidney stone in this imaging?
Uteropelvic junction
Pelvic inlet
Uterovesical junction
Where is a kidney stone in theis imaging?
Uteropelvic junction
Pelvic inlet
Uterovesical junction
Where is a kidney stone in theis imaging?
Uteropelvic junction
Pelvic inlet
Uterovesical inlet
Where is a kidney stone in theis imaging?
Uteropelvic junction
Pelvic inlet
Uterovesical inlet
Why might a non-contrast CT not show a kidney stone despite symptoms? [1]
When we do not find a shadow of a ureteral stone on the x-ray, this does not mean that there is no stone, as it depends on the percentage of the presence of calcium in the composition of this stone, as some types of stones do not give a shadow on the x-ray.