Kidney in Homeostasis Flashcards
What roles do the kidneys play a part in?
→ regulation of plasma [K+]
→ regulation of pH
→ excretion of nitrogenous waste
→ blood volume regulation
→ osmoregulation
→ regulation of plasma [Ca2+] & [Pi]
→ eryhtropoeitin production
→ gluconeogenesis
What problems does chronic kidney failure lead to?
- hyperkalaemia
- acidosis
- azotemia
- hypertension
- renal osteodystrophy
- anaemia
These happen due to dysfunction of excretory or endocrine roles of kidney.
Endocrine roles of the kidney
→ hypoxaemia
→ decreasing blood volume
→ increase parathyroid hormone, increase prolactin, increase growth hormone
→ erythropoietin
→ renin —> angiotensin II
→ 25-OH vitamin D3 —> calcitriol
Diabetic nephropathy
Mesangial cells proliferate in response to increased glomerular pressure.
Eventually leading to compression of glomerular capillaries and decreases in GFR.
- ↑ in glomerular capillary [glucose]
- Diffusion to proximal convoluted tube so increase in [glucose]pct
- ↑ glucose reabsorption
- ↑ NaCl reabsorption
- ↑ water reabsorption
- ↓ pressure in PCT
- ↓ flow to Macula Densa
- Tubuloglomerular feedback causes hyperperfusion which increase GC blood pressure which will cause renal damage
Tubuloglomerular feedback can cause further kidney damage:
→ renal damage
→ decreased GFR
→ (tubuloglomerular feedback)
→ afferent arteriole dilation/renin secretion
→ (Angiotensin II and aldosterone)
→ hypertension
→ increased glomerular pressure
→ renal damage
→ (loops)
You can treat this with ACE inhibitors like Ramipril.
Hypoxia induced EPO production
→ Hydroxylation of the transcription factor HIF-2a
→ Hypoxia prevents hydroxylation of the transcription factor HIF-2a
→ allowing EPO production
The kidneys play a key role in plasma acid-base balance
increased CO2 + H2O <—> HCO3- + increased H+
→ if you change the concentration of either CO2 or HCO3- in the blood
→ you will alter the pH of the blood stream
→ as predicted by the Henderson-Hasselbach equation
→ Metabolism form lots of volatile acid in the form of CO2
CO2 —> HCO3- + H+
The lungs can normally efficiently remove this.
Reflex increase in ventilation rate
Increase in firing of chemoreceptors:
→ Peripheral
→ (CNIX, CNX)
→ NTS
→ central pattern generator in brainstem
→ increased, more frequent phrenic and intercostal nerve activity
→ more forceful and frequent contraction of diaphragm/intercostal muscle
→ increased rate and depth of breathing (increased ventilation rate)
Central
→ straight to central pattern generator in brainstem and then same flow chart as peripheral
HCO3- reabsorption in PCT and TAL
→ Virtually all HCO3- is reabsorbed from nephron
→ HCO3- reabsorption in PCT and TAL
→ Carbonic anhydrase helps us reabsorb bicarbonate
→ CO2 can diffuse across membrane
→ HCO3- is converted into H2O and CO2 by carbonic anhydrase IV as CO2 can diffuse from lumen into interstitial cell
CO2 and H2O → H2CO3
→ by carbonic anhydrase II
→ H2CO3 then dissociates into H+ and HCO3-
→ the HCO3- which can then move with Na+ or against Cl- into the interstitium
→ HCO3- has been absorbed
HCO3- reabsorption in Type A intercalated cells in distal tubule and collecting ducts
Once the HCO3- is in the cell it can diffuse to the interstitium via Cl- exchange. There is Cl- channel pumping Cl- into interstitium so it can then go back into cell in exchange for HCO3-
K+ also has a channel pumping out to increase the rate of the Na+/K+ ATPase channel pump inning Na+ out and K+ in
Metabolisms forms non volatile acids that cannot be removed by the lungs
→ Lactic acid, phosphoric acid, sulphuric acid and ketone bodies
→ the GI tract absorbs more acid than bicarbonate
1.
→ Non-volatile acids are initially buffered in the ECF (principally by HCO3-)
→ Forms:
H+ + HCO3- <—> H2CO3 <—> CO2 + H2O
- → Lungs excrete acid in form of CO2
- → Buffers are regenerated by unloading the bound H+ to HCO3-
→ the kidney forms new HCO3- to replace what was lost
HCO3- production in PCT
→ Glutamine enters epithelial cell
→ glutamine transformed into a-ketoglutarate
oxaloacetate → phosphoenopyruvate → glucose → HCO3-
→ HCO3- formed as byproduct from glucose production
→ 3HCO3- moves out of cell into interstitium with Na+
→ Glucose will also move out of the cell into the interstitium
→ Glutamine in the cell causes NH4+ to dissociate into NH3 + H+
→ H+ will return back to the lumen in a Na+/H+ exchange and NH3 will diffuse back into the lumen here it will rejoin H+ and reform NH4+
How do we excrete the formed NH4+ from HCO3- production in PCT
→ some NH4+ reabsorbed by thick ascending limb
→ but this will dissociate and recycle efficiently back into nephron
→ eventually binds H+ and gets trapped inside collecting ducts before leaving in urine
Proton trapping of NH4+ in collecting ducts
→ in interstitium NH4+ dissociates NH3 + H+
→ the NH3 is taken into the cell, converted into NH4+ and then exits the cell into lumen as NH3
→ this NH3 will the rejoin H+ in the lumen and reform NH4+ again
→ the H+ in the interstitium is transported in as CO2 into cell which can then rejoin H2O to form H+ and HCO3-
→ H+ will then enter lumen and rejoin NH3 to form NH4+
In response to chronic acidosis the kidney can increase plasma [HCO3-]
Response to chronic acidosis:
→ liver reduces urea production and starts producing more glutamine
Response to chronic acidosis:
→ kidney produces more glutamate dehydrogenase and PECK
→ to catalyse breakdown of glutamine into NH4+and HCO3- in PCT
NH4+ lost in urine
Increase plasma [HCO3-]
Increase plasma pH
In response to chronic respiratory alkalosis the kidney can decrease plasma [HCO3-]
In response to chronic alkalosis:
→ there are increased numbers
→ increased activity of Type-B intercalated cells in the collecting ducts
→ these help secrete HCO3- into the tubule lumen - helping increase their concentration in the final urine
Decreased plasma [HCO3-]
Decreased plasma pH
Increase in HCO3- lost in urine
