Formation of urine 1 Flashcards
Overall function of proximal convoluted tubule
Reabsorption:
- water
- Ions
- all organic nutrients
Overall function of Loop of Henle
Descending limb- more absorption of water.
Ascending limb-
Absorption of NaCl
Overall function of distal convoluted tubule
Secretion:
- Ions
- Acids
- Drugs
- Toxins
Reabsorption:
- Water
- Na+
- Ca2+
Overall function of the collecting duct
Variable absorption of water
Reabsorption of:
- Na+
- K+
- H+
- HCO3-
Papillary duct
Section of the nephron that delivers urine to the minor calyx.
Two forces that drive filtration in the nephrons
Blood pressure
Differing diameter of afferent and efferent arterioles/ renal blood flow
GFR
Glomerular filtration rate
- The rate at which glomerular filtrate is produced.
- Normally 125mL/min
- Used as an indicator of renal function.
- Stays constant even when systemic BP changes due to autoregulation of renal blood flow
Ultrafiltration
- Definition
- Molecules filtered
- Things that stay in the blood
The filtration of the blood at a molecular scale.
Small molecules filtered:
- Electrolytes
- Amino acids
- Glucose
- Metabolic waste
- Some drugs and metabolites.
Cells and larger molecules stay in the blood.
- RBCs
- Lipids
- Large proteins
Sequence the filtrate passes through during filtration.
- Pores in glomerular capillary
- Basement membrane of Bowman’s capsule.
- Filtration slits in podocytes into the capsular space
Two forces that filter fluid out of the blood.
This is the Glomerular capillary hydrostatic pressure
- Filtrate leaving glomerulus into capsular space.
It is also the oncotic pressure of the Bowman’s space but this is almost 0.
Two forces that oppose ultrafiltration
Glomerular capillary oncotic pressure
Bowman’s capsule hydrostatic pressure.
Overall equation of net filtration pressure
[Glomerular capillary hydrostatic pressure]- [Bowman’s capsule hydrostatic pressure + Glomerular capillary oncotic pressure]
This decreases significantly at the end of glomerular capillary.
Autoregulation of renal blood flow
- hypotheses
In the kidneys, renal blood flow and GFR stay the same when blood pressure is 90-200 mmHg.
Not due to neuronal or hormonal response.
Two hypotheses for this mechanism:
- Myogenic: arterioles respond to stretch..
- Metabolic: renal metabolites modulate vasodilation
Change in GFR according to afferent and efferent arterioles
Afferent arteriole is usually wider than efferent.
To increase GFR:
- Afferent dilates and efferent constricts
- GFR returns to normal
To decrease GFR due to high BP:
- Afferent constrict and efferent dilates
Substances that dilate the afferent artery
Prostaglandins
ANP (atrial natriuretic peptide)
Dopamine
NO
Kinins
Factor that constricts the efferent arteriole
Angiotensin II
Decrease in GFR according to afferent and efferent arterioles
- Include what causes dilation and constriction
The afferent arterioles constricts and efferent arterioles dilates.
Constriction of afferent:
- Adrenaline
- Endothelin
- Adenosine
- ADH
Dilation of efferent:
- Adenosine
Explain how changes in GFR can alter system blood pressure
When blood pressure drops, filtration pressure drops:
- Decreases GFR
- Less Na+ is filtered
Less Na+ in proximal tubule is sensed by macula densa:
- Stimulates juxtaglomerular cells to release renin into the blood.
Renin release leads to Ang II release:
- Increases BP via vasoconstriction until it returns back to normal
Effects of angiotensin II in the RAAS
- Ions
- Water
- Blood pressure
- Hormone secretion
Increases sympathetic activity
Increases reabsorption of:
Na+
Cl-
Increase secretion of K+
Increases H2O retention.
Increases aldosterone secretion
Arteriolar vasoconstriction- increases BP
Stimulates ADH secretion
Increase H20 absorption in collecting duct.
Reabsorption at proximal tubule
The following are almost completely reabsorbed:
- Glucose
- Amino acids
- Filtered proteins
60-70% of the following: Water Na+ Cl- HCO3- K+ Urea
What protein drives reabsorption at the proximal tubule?
Na+/K+- ATPase
- 3 Na+ out of cells into blood
- 2+ K+ into cells
Na+ reabsorption at PT
Gradient for Na+ absorption is driven by Na+/K+ pump at basolateral membrane of tubular cells.
Na+ enter the cells via Na+/H+ pump.
- Also co-transported with Phosphate and sulfate ions.
Cl- follows reabsorption of Na+ through facilitated diffusion
Water reabsorption at PT
Movement of solutes out of the tubular lumen (Na+, Cl- and HCO3-) increases osmolarity of interstitial fluid.
This drives water out of tubular fluid into interstitial spaces via paracellular and transcellular (aquaporins) routes
- Aquaporins are on the basolateral and apical membranes
Aquaporin-1
Widely distributed aquaporin.
Abundantly found in the PCT.
Aquaporin-2
Aquaporin found on the apical surface of the collecting duct.
Controlled by ADH
Aquaporin-3 and Aquaporin-4
Aquaporin found on the basolateral surface of the collecting duct
Glucose reabsorption at the PT
Co-transported with Na+ into the tubular cell- apical membrane
- At PCT the co-transporter has high capacity and low affinity for glucose.
- At PST the co-transporter has low capacity and high affinity.
Moves down a concentration gradient.
Exits cell via basolateral membrane:
- GLUT-2 at PCT
- GLUT-1 at PST
This mechanism ensures very little glucose is excreted.
Transport maxima
Maximum transport capacity of glucose.
Maximum amount of glucose that can be reabsorbed at the PT. The rest is excreted.
Excess urinary excretion of glucose= diabetes
SGLT2
Na+/ Glucose co-transporter in the PCT.
- Low affinity
- High capacity
SGLT2 inhibitors
K+ reabsorption in the PT
70% absorbed- mainly down concentration gradient through tight gap junctions
Urea reabsorption in the PT
40-50% reabsorbed down conc gradient
Amino acid reabsorption in the PT
7 different transport processes, depending on amino acids.
High transport maxina
Protein reabsorption in the PT
Small amount of proteins reabsorbed enter the cell via pinocytosis.
They are enclosed in vesicles and degraded by lysosomes to release amino acid into the blood.
This method has a very limited transport maxima.
Secretion into the PT
Some drugs/ substances are to large or bound to proteins.
OAT and URAT pumps compounds from plasma to nephron.
OAT
Organic anion transporter.
Pump that moves substances from the blood into the lumen.
Located on both apical and basolateral membranes.
PAH
Para-amino hippourate.
Secreted into the PT with alpha-ketoglutarate or di/tricarboxylates- from the blood.
Transported out of PT cells in exchange with another anion into lumen.
Used to measure tubular secretion as it is not endogenous.
Endogenous acids secreted into the urine by PT (6)
cAMP
Bile salts
Hippurates
Urate
Oxalate
Prostaglandins
Endogenous bases secreted into the urine by PT (8)
Creatinine
Dopamine
Adrenaline + Noradrenaline
Histamine
Choline
Thiamine, Guadine
Acidic drugs secreted into the urine by the PT (7)
Acetozolamide
Chlorothiazide
Furosemide
Pencillin
Salicylate
Hydrochlorothiazide
Bumetanide
Organic basic drugs secreted into urine by the PT
Atropine
Isoproterenol
Cimetidine
Morphine
Quinine
SGLT2 inhibitors
‘Flozins’- Used to treat diabetes by increasing excretion of glucose
Dapagliflozin
Canagliflozin
Empagliflozin
