Kidneys Flashcards
Glomerular filtration rate and % of plasma filtered in glomerulus
The volume of fluid filtered into the glomerulus per minute.
Normal 125 ml/min. 20% of plasma
Renal clearance/ osmotic clearance and equation
Volume of blood cleared of a substance over time U x V / P
Osmotic clearance is the volume of plasma cleared of all osmotically active particles per unit time.
Renal plasma flow
Volume of plasma going into kidney over time 600 ml/min Renal blood flow = 1100 ml/min
Glucose reabsorption
Occurs in proximal convoluted tubule
Enters with sodium glucose cotransport
Exits with glut facilitated transport
Amino acid reabsorption
8 amino acid transporters, 6 of which sodium dependent
molecules that get reabsorbed via Na Coupled transporters and passive reabsorptions in the proximal convoluted tubule:
Urea, amino acids, phosphate, glucose, chloride, calcium, sulphate, potassium
Na Transporters: Glucose, amino acid, phosphate, sulfate
Passive diffusion: Urea, chloride, potassium, calcium
Secretion of organic acids anions (where how)
Proximal tubule
- Organic anion p enters in exchange for dicarboxylate through organic anion transporter
- OA enters tubule via ATP dependent transporters Dicarboxylate comes from sodium coupled Transporters
Organic cation secretion
Occurs in proximal convoluted tubule
- Enters via facilitated organic cation transporter (OCT2)
- Enters tubule via multi drug and toxin extrusion protein (MATE2-K/MATE1) in exchange for H+
Osmolality
Osmoles of solute per kg of solvent
measure of water concentration- if low, water is high
Normal urine osmolality
Normal plasma osmolality
Normal plasma sodium concentration
Urine: 50-1400 mosm/kg
Plasma: 285-295 mosm/kg
Sodium: 135 -145 mmol/l
Sodium reabsorption in proximal tubule
In: Na nutrient symporter, Na H exchanger
Out: Na/K pump Cl passively diffuses our
Sodium reabsorption thick and thin ascending limb
In: Na K CL cotransporter
Out: sodium potassium pump Cl passively diffuses out
Thin: passive diffusion
Sodium reabsorption distal tubule
In: Na Cl cotransporter
Out: sodium potassium pump Cl passively diffuses out
Sodium reabsorption in collecting duct
In: Na channel Out: Na k pump (principal cell)
In: Na/ H+ transport Out: Na K pump (intercalated cells)
Urea movement (pCT, Henle, CD) and effect of ADH on their reabsorption.
Proximal tubule: passive reabsorption
Loop of henle: apical secretion via urea transporter 2 (UT2)
Inner medullary collecting duct: apical reabsorption via UTA1
Net movement: 40 filtered is excreted, 60% reabsorbed\
ADH increases reabsorption
ADH action on collecting duct
ADH binds to V2 receptors on collecting duct, causing the activation of cAMP pathway and migration of aquaporin protein to luminal membrane Water can be reabsored through channels
Polyuria/ oliguria
Polyuria: excessive urine output
Oliguria: too low urine output -> less than .428L/day (obligatory water loss for all waste to be excreted)
Free water clearance calculation
Diuresis vs antidiuresis pathway
Production of ADH in posterior pituitary
Osmoreceptors in hypothalamus signal to magnocellular neurosecretory cells in paracentricular and supraoptic nuclei. These produce precursors to ADH that enter posterior pituitary and produces ADH
Effects of alcohol, nicotine BP and blood volume on ADH secretion
Alcohol inhibits ADH Nicotine stimulates ADH
BP: lower pB increases secretion
Volume: lower volume increases secretion
Neurogenic diabetes insipidus origins and what it is
excessive urination
No ADH secretion
Can be congenital or due to an injury
Nephrogenic diabetes insipidus origin and what it is
Excessive urination because no water reabsorption
Issue at level of kidney:
Inherited (mutated V2 receptor or aquaporin)
Acquired (infection or side effect of drug)
Mechanism of osmotic diuresis
Increased blood glucose
Increased glomerular filtration of glucose
Increased osmolality
Reduced reabsorption if water because smaller conc. gradient so greater water loss in urine
K reabsorption in proximal tubule
Passively diffuses out (channels)
K reabsorption in thick ascending limb and distal tubule
In: Na K Cl cotransporter
Out: facilitated diffusion In distal tubule via k H exchanger
K transport in collecting duct
Reabsorption in intercalated cells: k h exchanger K
secretion by principal cells
Out: k channels (ROMK, BK) and K CL co transporter
Factors affecting k secretion in principal cells of collecting duct (Na, aldosterone, tubular flow, pH)
- Factors affecting Na entry through ENaC channels (if more Na in cells, more k will flow out)
- Aldosterone stimulates k channels
- High tubular flow rate favors secretion (+ charges washed away in lumen so K+ has more space to go in)
- Acidosis inhibits, alkalosis enhances it
Hypokalemia causes and level at which it becomes hypokalemia
Main issues caused by hypokalemia
Less than 3.5mM
Resting membrane potential becomes more negative. So nervous symptoms (Cardiac, skeletal muscle, GI, renal)
Hyperkalemia causes and signs
- Decreased external loss (renal failure, hYpoaldosteronism) 2. Redistribution out of cells (acidosis, tissue destruction)
Can cause hyperreflexes, vomiting, nausea, dysrythmias because resting membrane potential is increaed so easier to depolarise cells.
Main solutes in body
Sodium, potassium, glucose
Pathways controlling sodium reabsorption
stimulate renin release (angiotensin)
aldosterone
atrial natriuretic peptide
dopamine
Causes of renin release (4) and where it is released from
Decreased sodium delivery to macula densa
Decreased wall tension in afferent arteriole (baroreceptors)
Sympathetic activity
Low blood volume
Released from juxtaglomerular cells
Formation of angiotensin
Plasma angiotensinogen -> angiotensin I (due to renin)
Angiotensin I (10 peptide) to angiotensin II (8 peptide) via converting enzyme.
Effects of angiotensin (5)
Effects of aldosterone
Stimulates expression of ENaC channels, ROMK channels and sodium potassium pumps in collecting duct principal cells.
Stimulates K secretion and sodium reabsorption
Natriuretic peptide (what they are and what they do)
Hormones released when the heart is stretched.
Natriuretic effects: Inhibit ENaC in collecting duct. (sodium reabsorption). Inhibits Na/K pump activity. Inhibit aldosterone production
Diuretic effects: Inhibit renin release
Hypotensive effects: Decrease blood pressure/ volume, vasodilate afferent arterioles
pH of buffer solution with Henderson hasselbach equation
pH= pK + log[HCO3]/[H2CO3]
Where bicarbonate reabsorption occurs
Proximal tubule Ascending loop of henle Cortical collecting ducts (intercalated cells)
HCO3 reabsorption
Bicarbonate is filtered in glomerulus
It binds to an H+ in lumen
It becomes water and CO2 and passively diffuses into interstitial cell
It can then be broken back down to H+ and HCO3- HCO3 is reabsorbed and H+ goes back into lumen
Importance of HCO3
It is an essential body buffer that binds with H+ to form water and CO2. CO2 can then be excreted by lungs.
H+ excretion
H combines with non bicarbonate ion and is excreted Or Glutamine in tubule enters epithelial cells and gets broken down to Nh4 nd bicarbonate. Bicarbonate is reabsorbed
Acute vs chronic respiratory acidosis
Acute: abrupt failure in respiration ph less than 7.35
Chronic: secondary to many disorders, less abrupt but longer lasting
Response to acidosis
Chemical (bicarbonate buffer)
Respiratory (to expel CO2)
Renal (increased glutamine metabolism, secretion of H + ions)
Response to alkalosis
Chemical buffers: some bicarbonate reacts with H+ to produce CO2, this gets rid of some bicarbonate but still causing pH to decrease.
Respiratory: reduce ventilation
Renal compensation: reduction in H secretion, bicarbonate is therefore excreted in urine. Type B intercalated cells also add H to blood using pendrin and CO2 and water
Structure of the glomerolus filtration membrane (3 layers) and role of this last layer.
- Widely fenenestrated capillary
- basement membrane (protein layer)
- podocytes and filtration slits. These serve to only let certain molecule sizes get through.
Cortical vs juxtamedullary nephrons
Cortical: mostly in the cortex, shorter loop of henle - produces more dilute urine
Juxtamedullary: longer loop of henle descending into medulla - produces more concentrated urine
Vasculature of the kidneys; pathway
Interlobular artery to glomerulus, the peritubular capillaries drain to interlobular vein.
Size of molecules at which filtration through bowman’s capsule becomes difficult
7kDa
Do anions of cations cross the glomerular filtration membrane better? Why?
Cationns: because negative charges fixed on basement membrane
How starling forces influence glomerular filtration rate
Starling forces:
- hydrostatic pressure: fluid pressure pushing it into glomerulus (can be controlled by vasodilation/ constriction of afferent and efferent arterioles)
- oncotic pressure: pressure generated by solvents pushing it into capillaries
How inulin is used to measure GFR and why it is good for this. What PAH is good for measuring
Inulin concentrations in urine and plasma over time can be used to measure clearance, which is equivalent to the GFR because:
It gets fully filtered at glomerus
Does not get secreted in proximal tubule
Does not get reabsorbed
Does not get metabolised
PAH gets fully secreted so it’s clearance is approx equivalent to Renal blood flow
Concept of countercurrent and how this explains water reabsorption and generation of a concentrated urine
In ascending limb of the loop of henle, Na is pumped out via triporter, which causes water in the descending loop to flow out to match this osmolarity. When it gets to the ascending loop, there is less of it but water cannot flow back in because ascending loop is impermeable to water. Water volume is therefore reduced.
Mechanism of Extrinsic control of GFR (when BP is too low)
Extrinsic: maintains arterial blood pressure by activation the sympathetic nervous system, which vasoconstricts the afferent arterioles. Also reduces filtration barrier via mesengial cells (
Intrinsic: Protexts renal capillaries from hypertensive damage and maintains healthy GFR
Reaction of carbon dioxide and water forming H+ and bicarbonate and what diahrrea and vomitus effects on these products
Important buffers in urine
Phosphate and ammonia
Role of glutamine as an additional mechanism for adding HCO3 to plasma
changes in these for the following disorders
