Kidney as a producer, excreter and regulator Flashcards
Erythropoeitin
- Produced when fall in oxygen levels
- Secreted by peritubular cells
- Stimulates RBC production
Vitamin D
- Skin + UVB = cholecalciferol
- Liver converts to calcidiol (25-hydroxycalciferol)
- Kidney: converted to 1,25-dihydryoxycalciferol
- Calcitriol increases Ca2+ by promoting GI absorption, decreasing renal excretion and stimulating bone reabsorption
How does fluid travel in nephron
Blood, PCT, LOH, DCT, CD
Tight junctions in PCT, DCT, CD
- Large number of proteins creates a barrier to water and dissolved particles
- Loose in PCT
- Tight in DCT
- Very tight in CD
Journey through nephron
- Afferent arteriole - Bowman’s capsule - filtrate - efferent removes unfiltered
- Nephron transmits between cortex and medulla
- Glomerulus - PCT - LOH - DCT - CT
Cortical glomeruli
Dilute but don’t concentrate
Function of inter medullary glomeruli
Concentrate and dilute
Podocytes
negatively charged, cover glomerular capillaries, have small filtration channels
Glomerulus
Produces filtrate by high pressure system
Anions pass less easily than cations
Na+, HCO3-, glucose but no proteins
What is GFR?
Marker of renal function
How to calculate rate of filtration
Urine flow x urine concentration
Markers of renal function
creatinine (product of muscle metabolism, slight overestimation), cystatin C (produced by most cells) and inulin (plant extract, infuse to steady state)
How to calculate GFR
(UFR x Cu) / Cp
Cu = creatinine in urine, Cp is creatinine in plasma
When will GFR be proportional to 1/Cp
Creatinine production constant
What happens when arterial pressure falls?
Drop in RBF and GFR
Arteriole dilates, improving RBF
Efferent arteriole constricts, improving GFR
Function of adenosine
produced in hydrated state, constricts afferent arteriole to reduce GFR and inhibit renin release, switched off with reduced filtrate flow
Function of angiotensin ii
produced from renin cascade, constricts efferent arteriole to maintain GFR, leads to ATII inihibition in hypovolaemia
Function of PGE 2
roduced in DCT when filtrate flow decreased, dilates afferent arteriole to maintain RBF, cytoprotective to tubule, antagonises vasopressin, beware NSAIDs in hypovolaemia
Two types of auto regulation mechanisms
Myogenic and tubule-glomerular feedback
3 types of tubule-glomerular feedback
Adenosine, angiotensin ii and PGE 2
Function of PCT
- Conservation of majority of useful filrate components
- Reabsorbs Na+, HCO3- and glucose and water
- At the end, [Na+] same as plasma, no HCO3- and no glucose
- H2CO3 breaks down to produce the proton
- Exchanges for Na+ in antiporter
- Sodium leaves, water follows
- Transport maximum of glucose is 2mmol/min, when this is reached, glycosuria results
Function of LOH
- Produced hypotonic tubular fluid and hypertonic interstitial fluid and some reabsorption of Na+, K+ and Cl-
- At the end, extremes in osmolality (medulla interstitium is very high and tubular fluid is very low)
- Mechanism: selective permeabilities to ions and water
- Ascending limb: impermeable to water but permeable to ions, causing high concentration of ions in interstitial space
- Fluid is progressively more dilute as you ascend
- Ion reabsorption in ascending limb: Na+/K+ co-transporter, K+ into blood, Na+ leaves
How does furosemide work
diuretic, blocks co-transporter of Na+ and K+ so none reabsorbed
Characteristics of descending limb
- Permeable to water, impermeable to ions
- Water is lost via AQP1
- Tubular fluid more concentrated coming down
Where does water move in LOH
From descending LOH to ascending limb of vasa recta
Why is water reabsorbed efficiently in CD
Hypertonic environment
Function of DCT
Final regulation of sodium, potassium, hydrogen
Function of principal cells
reabsorb sodium and secrete potassium, regulated by aldosterone
Function of intercalated cells
reabsorb potassium and secrete hydrogen, driven by ATPase
Stimuli of principal cells
Aldosterone, increased potassium, alkalosis, increased tubular flow
Stimuli for intercalated cells
Acidosis, decreased potassium
Function of CD
Final water regulation, regulated by ADH
Aquaporins
- Water channels
- Narrow shape and charged walls
- Positive in core
- Over 8 sub-types
Site and nature of AQP 1
Site = PCT, descending LOH basal membrane Nature = continuous water reabsorption
Site and nature of AQP 2
Site: CD
Nature: response to ADH, variable water reabsorption
Site and nature of AQP 3
Site: CD basal membrane
Nature: continuous water reabsorption
Site and nature of AQP 4
Site: CD basal membrane
Nature: continuous water reabsorption
How is water reabsorbed in CD
- ADH released from posterior pituitary in response to hypothalamic osmoreceptors
- ADH causes AQP2 to insert
- 3 receptors - all G-protein
3 receptor are V1a, 2 and 3
Where is H+ secreted and HCO3 absorbed
PCT
Which cells make final adjustments in DCT
Intercalated cells
How is H= secreted and HCO3 reabsorbed
H2CO3 forms H+ and HCO3-
H+/Na+ moves hydrogen into lumen and Na+ into tubular cells
Na+/HCO3- co-transporter moves into blood
Function of JGA
- Between afferent arteriole and DCT
- Senses decrease in pressure (granular cells) or decreased sodium tubular flow (macula densa cells)
- Triggering of this apparatus leads to dilation of afferent arteriole (decreased adenosine and PGE2) and releases renin (also triggered by B1 stimulation)
Function of AT 1
Acts on aldosterone = volume retention in kidneys
Function of angiotensin ii
Vasopressin - water retention (V2) and vasoconstriction (V1a)
Function of baroreceptors
Increase HR and vasoconstriction