Kidney Flashcards
What does the kidney excrete?
Urea and uric acid - protein catabolism
Creatinine from muscle creatine
End products of haemoglobin
Foreign chemicals eg drugs, pesticides
What body compositions does the kidney control?
Volume regulation - inked to Na concentration
Osmoregulation - linked to H2O
pH regulation
What hormones act on the kidney?
ADH aldosterone natriuretic peptides parathyroid hormone fibroblast growth factor 23
What hormones does the kidney produce?
renin vitamin D erythropoietin prostaglandins alpha-klotho
What are the parts of the renal corpuscle?
Fenestrated capillary endothelium
Basement membrane
Tubular epithelium (podocytes)
Capillary lumen
What are the two types of nephron?
Cortical (85%) - short loop of Henle
Juxtamedullary (15%) - long loop of Henle, producing concentrated urine
What are the names of the arterioles and capillary beds of the nephron?
Afferent and efferent
Glomeruli and peritubular
What are the three basic renal processes?
Glomerular filtration
Tubular secretion
Tubular reabsorption
What is glomerular filtration?
The movement of fluid and solutes from the glomerular capillaries into Bowman’s space, 20% of plasma that enters glomerulus is filtered
What is tubular secretion?
Secretion of solutes from the peritubular capillaries into the tubules
What is tubular reabsorption?
The movement of materials from the filtrate in the tubules into the peritubular capillaries.
What happens to para-aminohippuric acid in the kidney?
It is filtered by the glomerulus and secreted but not reabsorbed
Therefore is a measure of renl flow = 600ml/min
What happens to water and most electrolytes in the kidney?
It is filtered and some of it is reabsorbed
What happens to glucose in the kidney?
It is filtered and all reabsorbed
What gets through the glomerular filtration barrier?
Most parts of the plasma except proteins - all depends on molecular size, charge and shape
About 7kDa is max size for 100% filtration
What is glomerular filtration rate?
volume of fluid filtered fro glomeruli per minute
GFR depends on: starling forces, s.a of filtration area and hydraulic permeability of capillaries
What causes increased and decreased GFR?
Increased GFR - Constrict efferent arteriole
Dilate afferent arteriole and vice versa
What is the glomerular filtration per day?
180l/day - only 1.5l is urine per day though because of reabsorption
How is glucose normally reabsorbed?
Uses: SGLT-Na+-dependent glucoseco-transporter.
GLUT facilitated transporter.
Na+-K+-ATPase pump.
How are amino acids reabsorbed? What happens is this system goes wrong?
Reabsorbed via proximal tubule with at least 8 amino acid transporters - many Na dependent
Proteins get reabsorbed in PCT by endocytosis and are degraded to amino acids
Mutations in transporters can cause cystinuria (kidney cysteine stones)
What uses Na coupled transporters and what is passive reabsorption?
Na - glucose, amino acids, phosphate and sulphate
Passive - urea, chloride, potassium and calcium
How are anions secreted in proximal tubule?
Organic ion enters cell in exchange for dicarboxylate through transporters OAT1 or OA3
Dicarboxylate then accumulates in cells by metabolim and the transporters
Then anion enters tubule lumen via ATP dependent transporters
How are cations secreted in proximal tubule?
Cation eneters cell via transporters (OCT1)
Enter tubule lumen via multidrug and toxin extrusion proteins (MATES) antiporter in exchange for H+ or OCTN
Why does clearance of inulin measure GFR?
Freely filtered and isn’t reabsorbed, metabolised or secreted
What is used clinically and experimentally to measure GFR?
Experimentally - inulin
Clinically - creatinine (slightly secreted)
how much blood and plasma flow through the renal syatem per min?
Plasma - 600ml/min - plasma is 55% of blood vol.
So blood - 1100ml/min
What is osmolality?
A measure of water concentration - the higher the osmolality the lower the water conc.
Measured in mosm/kg
What is the main osmotically active solute in the body?
Sodium and is also involved in blood pressure
How is sodium reabsorbed in the kidney?
Loop of Henle - passive in thin ascending limb which has few mitochondria
Proximal tubule - Na/H exchanger, Na/K ATPase, Na nutrient symporter (65%)
Thick ascending limb - Na/K/2Cl co-transporter, Na/K ATPase, K channel (25%)
Distal tubule - Na/Cl co-transporter, Na/K ATPase (2-5%)
Collecting duct - Na channel, Na/K ATPase (5%)
How is concentrated urine produced?
Na and H2O reabsorption is separated
Renal medulla interstitial fluid has high osmolarity to drive water reabsorption
At Henle’s loop more salt is reabsorbed (25%) than water (10%)
How does the ascending tubule allow sodium to be reabsorbed but not water?
Ascending tubule is impermeable to water
But contains Na/K/2Cl co-transport so Na can leave tubule to be reabsorbed
How does descending tubule allow water to be reabsorbed and picks up salt?
NaCl is picked up through passive diffusion
H2O is reabsorbed through Aquaporin-1 water channels
What parts of the loop of Henle have what sort of fluid?
The left of the descending limb is high in H2O, the centre between the two tubes is full of NaCl
How is urea recycled by kidney?
Proximal tubule - passive reabsorption
Loop of Henle - secretion (60%) via urea transporters (UT-A2)
Inner medullary collecting duct - apical reabsorption via UT-A1
40% of that filtrate is then secreted
ADH enhances reabsorption using UT-A1 and UT-A3 in the collecting duct
What is the vasa recta?
Capillaries that lie next to collecting duct - supplies blood without washing away the gradient and take water away from the medulla
How many waste products are produced each day and what is the max. conc. of urine?
waste: 600 mosmol/day
max. conc. 1400 mosmol/l
What is the clinical name for reduced water in urine?
Oliguria
What is the clinical name for excessive urination?
Polyuria
Why is ADH effective at changing urine conc.?
Short plasma half life (10-20 min)
Fast acting
How does blood pressure affect osmolality and ADH release?
The more ADH in the body, the higher blood pressure and volume will be but also the higher osmolality will be
Angiotensin II increases ADH secretion and natriuretic peptides decreases ADH secretion
What can affect ADH levels?
Inhibits ADH: Alcohol
Stimulates ADH: Nicotine, Nausea, Pain and Stress
What happens in diabetes insipidus?
Polyuria, polydipsia and nocturia
Neurogenic (no ADH secreted) - brain trauma or congenital
Nephrogenic - inherited (mutated V2 receptor or aquaporin 2 channel), acquired (effect of drug eg. lithium)
What is osmotic diuresis?
Causes polyuria and polydipsia - ↑urination due to small molecules in renal tubule lumen, often happens in untreated diabetes mellitus
↑osmolarity in filtrate causes ↓water reabsorption from proximal tubule and later parts of nephron can’t compensate
How is potassium reabsorbed?
95% of potassium is reabsorbed
65% is reabsorbed passively at proximal tubule
30% is reabsorbed at thick ascending limb by Na/K/Cl co-transporter
Also reabsorbed by distal cells and intercalated cells but this is outweighed by secretion by principal cells through K channels or K/Cl co-transporter
What affects K secretion by principal cells in collecting duct?
Factors affecting Na entry through epithelial Na channels
Aldosterone stimulates K channels
High tubular flow rates favour secretion
Acidosis inhibits k secretion, alkalosis increase it
What is hypokalaemia (plasma K <3.5mM)?
Causes: ↑external losses eg. diarrhoea, vomiting, diuresis, sweat
Re-distribution into cells - metabolic alkalosis
Inadequate K intake - starvation and prolonged fasting
Symptoms: paralysis, vomiting, polyuria, heart dysrhythmia
Cure: eat high potassium food, use KCl drip, K sparing diuretics eg spironolactone inhibits aldosterone
What is hyperkalaemia?
Causes: ↓external losses - renal filure or use of drugs
Redistribution out of cells - acidosis, made worse by lack of insulin in diabetic ketoacidosis
Symptoms: Weakness, paralysis, dysrhythmias, nausea, vomiting
Treatment: stabilise cardiac membrane using Ca2+ drip
Insulin administered to move K+ into cells
↑K+ excretion with diuretics or treat renal failure
Which osmoreceptors are involved in the release of ADH and thirst?
Supraoptic and paraventricular nuclei - ADH release suppression
Lateral pre-optic area - thirst/non-thirst
How is ECF volume controlled?
Osmolality (water conc) of ECF is tightly controlled so volume is controlled by total quantity of solute (mainly sodium balance)
What is the body extracellular volume?
plasma - 4l
interstitial water - 10l
intracellular water - 28l
What does GFR depend on?
Starling forces (hydrostatic and osmotic)
Hydraulic permeability
Surface area
What is the auto-regulation?
Myogenic response by the renal smooth muscles that surround arterioles (vasoconstriction in response to stretch)
Tubuloglomerular feedback by the juxtaglomerular apparatus (controls vasoconstriction and renin release)
What controls Na reabsorption?
NaCl conc. receptors within macula densa
Pressure in central arterial tree
Presssure in renal afferent arterioles
Renal receptors in cardiac atria and intrathoracic veins
Renal sympathetic nerves (stimulate renin release)
Direct pressure effect on kidney
Renin/angiotensin II/aldosterone (stimulate Na+ reabsorption)
Atrial Natriuretic Peptide (causes natriuresis, inhibits Na+ reabsorption)
Dopamine (causes natriuresis, inhibits Na + reabsorption)
What causes a release of renin?
↓sodium delivery to macula densa
↓wall tension in afferent arteriole (intrarenal baroreceptor)
sympathetic activity
can be caused by hypovolemia (low blood volume)
How does angiotensin II stimulate proximal tubule Na reabsorption?
Angiotensin II binds to AT1 receptors so Na/K-ATPase releases Na out of the cell
What is the role of aldosterone?
↑Na reabsorption in DCT and CD and also sweat gland and salivary glands
↑Na absorption from gut
Where is aldosterone secreted from?
Zona glomerulus in adrenal cortex
