Renal Flashcards
What are the two theories of auto regulation?
Metabolic (metabolites cause vasodilation)
Myogenic -smooth muscle contracts harder when stretched more.
What is autoregulation?
Vasoconstriction or vasodilation in response to a change in BP to maintain filtration pressure.
What is tubulogloermular feedback?
The contents of the tubule reflect filtration and reabsorption. This is monitored in the distal convoluted tubule and the info is transmitted back to the glomerulus where the GFR can be modified.
What is the macula densa?
Part of the juxtaglomerulus apparatus in the distal tubule which monitors sodium and calcium levels in the tubule.
What does the macula densa do if the GFR is too high?
Promotes afferent vasoconstriction
What is the vasa recta?
Blood supply to the medulla of the kidney
Does the medulla of the kidney have a high or low oxygen consumption?
High
What may be the result of obstruction to the vasa recta?
Ischaemia in the tubule.
What is paradoxical vasoconstriction?
Blood is shifted away from the part if the medulla where there is an obstruction in the vasa recta.
This will increase hypoxia and may lead to acute kidney injury.
What makes up the filtration surface in the glomerulus?
Capillary endothelial cells with fenestrations.
Basement membrane
Podocytes with filtration slits.
What is a podocyte?
A modified epithelial cell with foot processes (pedicels)
What are the gaps between foot processes called?
Filtration slits
What is the passage of filtration in the glomerulus dependent upon?
- Molecular size
2. Charge
What charge does the BM have?
Negative
What is the effect of a negatively charged BM on filtration?
Big repulsion of larger negative molecules (eg albumin)
Less of a repulsion on smaller negative ions (eg Cl-)
What is GFR?
GFR = net filtration pressure x water permeability x area of filter
What is net filtration pressure?
Net filtration pressure = (capillary hydrostatic pressure - tubule hydrostatic pressure) - (plasma oncotic pressure - filtrate oncotic pressure)
What is the result of afferent vasoconstriction in the nephron?
Dec. glomerular blood flow
Dec. glomerular pressure
Dec. GFR
What causes afferent vasoconstriction in the nephron?
SNS
Adenosine
What is the result of afferent vasodilation in the nephron?
Inc. glomerular blood flow
Inc. glomerular pressure
Inc GFR
What may cause afferent vasodilation in the nephron?
NO
Prostaglandins
What is the result of efferent vasoconstriction in the nephrons?
Dec. blood flow out of nephrons
Inc glomerular pressure
Inc GFR
What is the result of efferent vasodilation in the nephrons?
Inc blood flow out of the glomerulus
Dec glomerular pressure
Dec GFR
What are mesangial cells?
Cells in the glomerulus which supports the glomerular filter, can contract to alter SA and is phagocytotic.
What is the filtration coefficient? (Kf)
The membranes permeability to water, dependant upon glomerular permeability and surface area.
How is the surface area in the glomerulus modified?
Contraction of Mesangial cells
What causes contraction of mesangial cells?
Ang2, NA, ADH
What causes relaxation of mesangial cells?
Prostaglandins
What is SNGFR?
The GFR of a single nephron.
What is the relationship between GFR and SNGFR?
GFR is the sum of all of the SNGFRs.
What defines chronic kidney disease?
Permanent loss of nephrons
What is the result of a decreased number of functional nephrons?
Hypertrophy of the remaining tubules and blood vessels, leading to hyperfiltration.
What is hyperfiltration?
When there is hypertrophy of tubules and vasodilation, which temporarily increases the GFR.
What is the problem with hyperfiltration?
It’s benefits are short lived. It causes glomerulosclerosis which causes more damage to the kidneys.
What is renal clearance?
The volume of plasma that is completely cleared of a marker substance per unit of time.
What are some important characteristics of a GFR marker?
Non toxic
Doesn’t affect the GFR
Not absorbed, metabolised or secreted
Easy to measure
What markers are used to study GFR clearance?
Inulin and Creatinine
What equation represents the clearance of a marker?
(Urine[marker] x volume) / (plasma[marker] x time)
When does clearance equal the GFR?
When none of the marker is reabsorbed, secreted or metabolised.
What is Inulin?
A ‘perfect’ GFR marker, however, it is exogenous and time consuming
What is creatinine?
A substance formed at a constant rate in the muscle.
What are plasma creatinine levels dependent upon?
Body muscle mass
Therefore, age and gender impact
Why is creatinine excretion slightly higher than creatinine filtration?
Some creatinine is secreted into the tubule.
How much of the filtered urea is cleared?
About 60% (the rest is reabsorbed)
What affects the plasma urea concentration?
GFR and hydration (dehydration leads to more urea in plasma)
If the GFR decreased, what would be the expected findings of urea and creatinine?
They should increase in parallel to each other
What is renal plasma flow?
The total volume of plasma to flow into the kidney.
How do you measure the amount of marker substance which is entering the kidney?
Renal plasma flow x plasma marker concentration
What is a hypotonic solution?
A solution that is less concentrated than the cell
What is a hypertonic solution?
A solution that is more concentrated than the cell
What are the 2 types of nephron?
Cortical and Juxtamedullary
What happens in the proximal convoluted tubule?
Obligate reabsorption and secretion
What happens in the loop of henle?
A cortical-medullary gradient is formed
What happens in the distal convoluted tubule?
Regulated reabsorption and secretion
What happens in the collecting duct?
Regulated reabsorption of water
In the proximal tubule, what exchange of ions occurs?
Glucose and sodium are co transported into the epithelium
Sodium and amino acids are co transported into the epithelium.
Sodium is also exchanged with H+, causing sodium to move into the epithelium.
Amino acids and glucose move passively from the epithelium to the interstitial space.
Potassium is transported into the epithelium from the interstitial space by active symport with sodium (using ATPase)
What is the renal threshold?
How much glucose it takes to saturate the glucose transporters
How much glucose is reabsorbed in the proximal tubule?
All of it!
How much bicarbonate is reabsorbed in the proximal tubule?
90%
What happens to metabolites in the proximal tubule?
Metabolites are secreted into the proximal tubule so they are removed from the blood faster than if they were just filtered.
What happens in the thin descending limb of the loop of henle?
Water is drawn out along an osmotic gradient
What happens in the thin ascending limb of the loop of henle?
Na+ and Cl- diffuse out.
What happens in the thick ascending limb of the loop of Henle?
Na+ and Cl- are actively pumped out by a Na+/K+/Cl- cotransporter
What do loop diuretics do?
Secreted in proximal tubule, act inside thick ascending limb by blocking the Na+/K+/Cl- cotransporter, preventing an osmotic gradient from forming, thus stopping water reabsorption in the collecting duct.
Is the medulla of the kidney hyperosmolar or hypo osmolar?
Hyperosmolar (due to loop of henle)
What causes the collecting duct to be permeable to water?
ADH release
What is ADH?
Anti Diuretic Hormone (vasopressin) secreted from pituitary gland
Causes an increase in water reabsorption
What causes the secretion of ADH?
Osmotic stimuli Exercise Pain/stress Nicotine and morphine Ang2
What decreases ADH secretion?
Alcohol and ANP
How does ADH increase the permeability of the collecting duct?
Increases aquaporins (water channels in the membrane)
What is Diabetes Insipidus?
Lack of ADH activity causing increased urination and an inability to concentrate urine.
What is polyuria?
An Increased urine production.
What are the 3 different types of Diabetes Insipidus?
Central - inadequate synthesis/secretion of ADH
Nephrogenic - kidney is unable to respond to ADH
Pregnancy - increased metabolic clearance of ADH
What regulates the collecting duct’s permeability to urea?
ADH. Urea is reabsorbed
What causes plasma urea concentration to increase?
Increased ADH or renal failure
What does a proportional increase in urea and creatinine suggest?
Renal failure
What does a disproportionate change in urea:creatinine suggest?
Dehydration or an increase in protein turnover
Where does the majority of sodium reabsorption occur?
Proximal convoluted tubule
Where does sodium reabsorption occur?
Proximal tubule, thick ascending limb, distal tubule and early collecting duct
What is ANP?
Atrial Natriuretic Peptide
What regulates sodium reabsorption?
Aldosterone and ANP
What are the 2 types of cell in the early collecting duct?
Principal cells (passive Na+ reabsorption and K+ secretion)
Intercalated cells (H+ secretion)
Where does Aldosterone work, and what happens?
Collecting duct! Promotes Na+ retention and K+/H+ secretion.
Principal cells - increases Na+ and K+ channels
Intercalated cells - increases Na+/H+ symporter
What type of drugs are Aldosterone antagonists? Give an example.
Potassium sparing drugs e.g. Amiloride
What happens in hyperkalaemia?
Membrane potential is increased which may lead to sudden cardiac death
What is hypokalaemia?
Membrane potential decreases which leads to muscle weakness and arrhythmias
How are proteins filtered?
Some small proteins may cross as part of glomerular filtration.
Epithelial cells in the proximal tubule engulf proteins, break them down into AAs and release them into the blood
What is proteineuria?
Lots of protein in the urine
What causes proteineuria?
Tubular disease
Glomerular leakage
Renal damage
What are the 3 types of proteineuria?
Glomerular proteineuria
Tubular proteineuria
Overflow proteineuria
What is glomerular proteineuria?
Excess protein in urine due to increased glomerular permeability
(Perhaps caused by BM damage and high capillary pressure)
What is tubular proteineuria?
Impaired reabsorption of protein (kidney damage)
What is overflow proteineuria?
Overproduction of small proteins
How does glomerular proteinuria occur?
Inc capillary pressure causes an increase in protein filtration.
BM loses its negative charge
Podocytes fuse and filtration slits enlarge
What is nephrotic syndrome characterised by?
Proteinuria and oedema
What is nephrotic syndrome characterised by?
Inflammation (protein and blood in urine)
What is microalbuminuria?
Increase in albumin excretion - first sign of diabetic nephropathy.
Not detected by dipstick.
What is orthostatic proteinuria?
Proteinuria, but only when upright!
Where is the H+ buffering in the kidney?
Distal nephron
What is shock?
A chronically low BP which leads to poor organ perfusion
How is venoconstriction used to increase cardiac output?
Venoconstriction causes raised venous pressure. RV preload increases = inc stroke volume and CO
What is internal transfusion?
Fluid moves from the interstitial space into the capillaries to increase the blood pressure
What is the acute response to shock?
Fast increase in BP to maintain perfusion
What is the long term response to haemorrhage?
Slowly replaces lost blood volume
What happens in prolonged shock?
Organ failure
Decreased sympathetic outflow, build up of metabolites = decreased BP.
DOWNWARDS SPIRAL!!
What replacement fluids are used after a haemorrhage?
Blood
Colloids (stay in capillaries and holds water there)
Crystalloids (dextrose goes into cells and takes water with it. Saline increases extra cellular volume)
How does shock lead to acidosis?
Shock - hypoxia - anaerobic metabolism - lactate - lactic acidosis
