5.2 Renal Flashcards
Kidney produces wha
The kidney is responsible for the manufacture of renin which acts on the circulating peptide angiotensinogen to convert it to angiotensin I which is then further cleaved in the lungs to angiotensin II. This acts on the adrenal cortex to release aldosterone.
1,25-dihydroxycholecalciferol (1,25-D), the active metabolite of vitamin D is formed in the kidney from 25-hydroxycholecalciferol(25-D). 1,25-D may also be produced by other cells in some pathological conditions (sarcoidsosis, tumours). Hypocalcaemia occurs in chronic renal failure and the kidney is also responsible for the synthesis of erythropoietin
GFR Measures
GFR measurements are made using renally inert indicators e.g. inulin, where passive rate of filtration at the glomerulus = rate of excretion. The normal value would be around 180 litres per day.
Renal blood flow will alter GFR but does not need to be measured.
Na reabsorption leads to a low excretion rate and low urine concentration and therefore use as an indicator would lead to an erroneously low GFR.
Tubular secretion would result in the clearance value being higher than that of inulin. It will be due to either tubular reabsorption or because the solute is not freely filtered at the glomerulus.
What weight substance freely filtered into glomerulus
Substances with a small molecular weight (MW) below 30,000 Da are freely filtered by the glomerulus. The glomerular filtrate will contain the same concentrations of electrolytes, glucose and aminoacids.
Proteins such as albumin (MW 70,000 Da) are filtered in very small quantities.
The other important factor influencing passage of substances is electrical charge. The basement membrane and podocytes are negatively charged and repel similarly charged molecules. Negatively charged molecules are therefore less able to pass across. The loop of Henle, distal convoluted tubule and the collecting ducts will not contain glucose because reabsorption would have occurred in the proximal convoluted tubule.
The electrolyte composition of other parts of the nephron would not match that of plasma because of varying degrees of water and electrolyte reabsorption.
Hyperchloraemic met acidosis
What type of AG
Is a.w ?
Hyperpara
panc fisutal
second hypoaldo
salicylate
A hyperchloraemic metabolic acidosis is associated with a normal or reduced anion gap (not raised).
Hyperparathyroidism is associated with this disorder.
Pancreatic fistulae are associated with bicarbonate loss.
Secondary hyperaldosteronism is often found in association with cirrhosis and is associated with a raised anion gap.
Salicylate poisoning is usually associated with an initial respiratory alkalosis followed by a metabolic acidosis.
Normal GFR
is a drug excreted by filtration - not absored - whats the max rate
If a drug is primarily eliminated by renal glomerular filtration (and not secreted or reabsorbed by the renal tube) it has the physiological characteristics to enable the measurement of glomerular filtration rate.
The gold standard for the measurement of glomerular filtration rate (GFR) is the use of inulin as a marker. The approximate value for a normal GFR is 125 mL/minute.
Filtered sodium reabsorbed where and how proportionally
Is creatine a good estimate of GFR
What is aldosterone
what does it do
What can cause type 1 renal tubular acido
what can cause type 2
How are they treated
Effect PTH on Phosphate
Nearly 99% of filtered sodium is reabsorbed by the kidney. Na+ reabsorption occurs at the following points:
Proximal tubule: 60-70% is antiported with H+ ions and organic molecules
Thick ascending loop of Henle 25% by Na+/K+/2Cl- co-transporter system
Distal tubule: 5% by Na+/Cl- co-transporter system
Cortical collecting duct: 2%
Creatinine is secreted into the proximal tubule, which is why it isn’t a perfect estimate of the glomerular filtration rate (GFR).
Aldosterone is a mineralocorticoid and acts on cells in the distal convoluted tubule and cortical collecting ducts, promoting sodium retention. There is some evidence that they cause a small amount of sodium reabsorption from the bladder.
Distal tubular dysfunction may lead to type 1 renal tubular acidosis, whereas proximal tubular dysfunction may lead to type 2 renal tubular acidosis. Both of which can be treated using oral sodium bicarbonate.
Parathyroid hormone (PTH) increases the clearance (excretion) of phosphate (not decreases) which may indirectly increase the mobilisation of calcium from bone.
What is clearance ml min of glucose inulin pah
What is inulin
What is pah
How is glucose handled in the glomerulus
The parameters of renal plasma flow (RPF) and glomerular filtration (GFR) rate in this question are normal. The filtration fraction (GFR/RPF=0.18) is also normal.
Clearance (mL/minute) Glucose 0 Inulin 125 Para amino-hippuric acid (PAH) 625 Drug A 50 Glucose is freely filtered by the glomerulus and is actively transported into plasma in the proximal convoluted tubule. Provided the active transport maximum (Tmax) has not been reached, the clearance will be 0mL/minute.
Inulin is a polysaccharide derived from plants. It is freely filtered by the glomerulus and is not reabsorbed or secreted by the renal tubules. These properties make it the ideal substance to measure glomerular filtration rate, normally 125mL/minute.
Para-aminohippuric acid (PAH) is freely filtered by the glomerulus but not reabsorbed by the renal tubules. Any left in the peritubular capillaries is secreted into the proximal convoluted tubules. This marker is used in the measurement of renal blood flow. Normal renal blood flow is in the order of 635mL/minute.
Drug A must lie somewhere between glucose and inulin. It is freely filtered but like urea does undergo some tubular reabsorption.
If drug A underwent intrinsic biotransformation in the kidney or liver, renal clearance would be 0 mL/minute.
ADH action
main action
what type of water
What does it do to the urine osmolality
What blunts affects adh
primary site is where
ADH’s major action is to increase reabsorption of osmotically unencumbered water from the glomerular filtrate and decreases the volume of urine passed. Increasing water reabsorption increases the osmolarity of urine to a maximum of four times that of plasma (approx 1200 mOsm/L).
Lithium, along with chronic water loading, potassium deficiency and cortisol and calcium excess, all blunt the action of ADH. This can lead to nephrogenic diabetes insipidus.
Its primary site of action is in the distal tubule and collecting duct.
GFR determines what
How was it oringally determined
Creatinine
How is that handled in glomerulus
why is it not a perfect measure
Glomerular filtration rate (GFR) is often measured to determine renal function and is defined as the volume of fluid filtered by the renal glomerular capillaries into Bowman’s capsule per unit time.
GFR was originally determined by injecting inulin into the plasma. Since it is not reabsorbed or secreted by the kidney after glomerular filtration, its rate of excretion is directly proportional to the rate of filtration of water and solutes across the glomerular filter.
Creatinine is an endogenous molecule, synthesised in the body and freely filtered by the glomerulus (it is also secreted in small amounts by the renal tubules). Thus creatinine clearance is a close approximation to the GFR.
The units of GFR are ml/min and the normal range varies slightly between males and females (males 97-137 ml/min and females 88-128 ml/min).
GFR is increased in pregnancy and during exercise.
The tubular secretion of creatinine is decreased by cimetidine, procainamide, quinidine and certain antibiotics.
Why is urine its colour
abnormal thing in urine
what can propofol do to urine
what is nroaml urine output
what is oliguria
Urine is coloured yellow by the pigments urochrome and uroerythrin, but it darkens on standing due to the oxidation of urobilinogen to urobilin.
Abnormal constituents of urine include
Glucose Ketones Bilirubin Erythrocytes Large numbers of leucocytes and Casts. The urine of patients on long term sedation using propofol is frequently coloured green.
Normal urine output in temperate climates is 800 - 2500 ml per day, which is about 1 ml/kg per hour. Despite the concentrating ability of the kidney, a minimum of 500 ml/day is required to eliminate the urea and other electrolytes.
Oliguria is defined as a urine production < 0.5 ml/kg per hour (approximately less than 50 mls), and may indicate hypovolaemia or renal failure.
Over what level can rbf autoreg
what are the mech
The renal blood flow can be maintained between a mean arterial pressure (MAP) of 80 mmHg and 180 mmHg.
There are two main mechanisms of renal autoregulation, these are:
Myogenic response; is the function of vascular smooth muscle to contract in response of a stretching force. This is thought to be due to an influx of Ca2+ into the myocytes activated by stretch dependent voltage-gated ion channels.
Tubuloglomerular feedback (TGF); this mechanism leads to the constriction of the pre-glomerular afferent arterioles in response to an increase in luminal concentrations of Na+ in the macula densa of the distal convoluted tubule.
An increase in arterial pressure will enhance tubular flow and improved glomerular filtration rate and reduced proximal tubular reabsorption.
Renal autoregulation minimises the impact of changes in arterial blood pressure on Na+ excretion.
Autoregulation is well preserved in denervated kidneys.
The effect of a fall in mean arterial pressure to the range 80-100 mmHg is likely to cause an increase in renal blood flow and a fall in renal vascular resistance.
Loop of Henle - tonicity compare plasma
what sate does it enter distal tubule
is the thick and thin limb permeable to water
what is the thick limb responsible for
what about thin limb
how much reach medulla
what about long loops
what are osm concentrationat various point
Fluid entering the loop of Henle is isotonic compared with plasma but it enters the distal tubule in a hypotonic state. Both the thick and thin ascending limbs are impermeable to water.
The thick ascending limb is primarily responsible for the extrusion of sodium as the thin ascending limb has little Na+/K+ ATPase activity.
Eighty five percent of nephrons (cortical) have short loops of Henle that barely reach the medulla. Only 15% (the juxtamedullary nephrons) have long loops.
The filtrate in the descending portion of the loop of Henle in the cortex and outer medullar have osmolarities of between 400 and 600 mOsm/L
The filtrate in the ascending portion of the loop of Henle in the cortex and outer medullar have osmolarities of between 200 and 400 mOsm/L
The filtrate in the portion of loop of Henle in the inner medullar has an osmolarity of approximately 1200 mOsm/L
ANP affect on kidneys
how man AA
why is it secreted
what does it do
what does it inhibt
how does it affect rbf & GFR
Natural atrial natriuretic peptide (ANP) is a 28 amino acid polypeptide hormone that is secreted by the cardiac atria in response to discharge from low volume stretch baroreceptors.
ANF is a physiological regulator of glomerular filtration rate (GFR) and mediates nephron hyperfiltration and natriuresis when salt excretion is threatened by a fall in the number of functioning nephrons.
It is a powerful inhibitor of renin secretion and aldosterone production.
It causes a decrease in afferent arteriolar resistance and in doing so it increases renal blood flow and a marked increase in glomerular filtration rate in the face of a slight reduction in filtration fraction. It also increases the efferent vascular resistance, which also increases the glomerular capillary pressure and filtration fraction.
act medullary cd = na excret
increase gfr = aff art dilat
promot flow to vr
Normal CBF
The normal cerebral blood flow is 54 ml/100g/minute.
Cerebral perfusion pressure (CPP) = mean arterial pressure (MAP) − intracranial pressure (ICP).
Typical values are: MAP = 90 mmHg and ICP = 12.
Normal CPP ranges between 75-85 mmHg.
Although the liver constitutes 2.5% of total body weight it receives almost 25% of the cardiac output.
The liver has a dual blood supply:
Hepatic artery 500 ml/min (100 mmHg), 95% oxygen saturation
Portal vein 1000 ml/min (7 mmHg), 70% oxygen saturation.
The coronary, renal and cerebral circulations are capable of autoregulation.
Drug idiosyncracies when it comes to hyponatraemia
tidy up this*******
This patient has a significant hyponatraemia. It is sufficiently low to give rise to clinical manifestations.
The symptoms and signs of hyponatraemia are mainly neurological and are related both to the severity and in particular to the rapidity of onset of the change in the plasma sodium concentration.
Patients may also have symptoms related to concurrent volume depletion and to possible underlying neurologic disorders that predispose to the electrolyte abnormality.
125 - 130mmol/L - Nausea and malaise
115 - 125mmol/L - Headache, lethargy, seizures and coma
<120mmol/L - Up to 11% present with coma.
The thiazide diuretics act on the distal convoluted tubule; as a result, they do not interfere with medullary function or with ADH-induced water retention.
In vitro data indicate that thiazides increase water permeability and water reabsorption in the inner medullary-collecting duct, an effect that is independent of ADH. In addition to water retention, the combination of increased sodium and potassium excretion (due to the diuretic) and enhanced water reabsorption (due to ADH) can result in the excretion of urine with a sodium plus potassium concentration higher than that of the plasma. Loss of this fluid can directly promote the development of hyponatraemia independent of the degree of water intake.
Ramipril and other ACE inhibitors may rarely cause severe hyponatraemia. The mechanism for this is unclear.
The normal response to hyponatraemia is to suppress ADH secretion completely, resulting in the excretion of a maximally dilute urine with an osmolality below 100 mOsm/kg of water and a specific gravity of 1.003 or lower. Higher values indicate an inability to excrete free water normally that is generally due to the continued secretion of ADH.
Most hyponatraemic patients are unable to produce dilute urine, and their urine osmolality may be 300 mOsm/kg of water or even greater. In those patients with hyponatraemia and a low plasma osmolality, the urine osmolality can be used to distinguish between impaired water excretion and primary polydipsia, in which water excretion is normal but intake is so high that it exceeds excretory capacity. In patients with impaired water excretion due to hypovolaemia the urine osmolality often exceeds 450 mOsm/kg of water.
In the absence of adrenal insufficiency or hypothyroidism, the two major causes of hyponatraemia with hypo-osmolality and inappropriately concentrated urine are volume depletion and the syndrome of inappropriate ADH secretion (SIADH). These disorders can usually be distinguished by measuring the urine sodium concentration, which is typically below 25 mmol/L with volume depletion and above 40 mmol/L in patients with SIADH.
Whilst the degree of hyperglycaemia and uraemia and dehydration alone might not contribute to this patient’s clinical state, they are contributing factors.
causes of alkalosis?
Anxiety is associated with hyperventilation and a respiratory alkalosis.
Cardiogenic shock would be associated with a metabolic and respiratory acidosis (not alkalosis).
Diuretics and primary hyperaldosteronism are also associated with metabolic alkalosis.
Pyloric stenosis is associated with vomiting and acid losses thus a metabolic alkalosis.
RBF normally
how can rbf est
which received higher rbf cortex or medulla
what increase corticla flow but reduces medullary
what is the effect of vaso
rbf & hypoxia
Renal blood flow (RBF) is normally 1200 ml per minute or approximately 25% of the cardiac output.
The Fick principle is used to estimate RBF
The cortex receives a higher RBF than the medulla, as one might expect with the increasing glomeruli in this region.
Prostaglandins increase cortical blood flow and reduce medullary blood flow.
Vasopressin causes renal vasoconstriction, especially cortical vasoconstriction.
RBF should increase in response to hypoxia.
How does the loop of henle work
what conditions does this provide
where is the active component
how does that work
where in the loop is permeamble to NaCl and H20
The loop of Henle employs a sodium counter-current mechanism to provide hypertonic conditions - approximately 1200 mmol/l, mainly sodium chloride and urea - in the deep medulla of the kidney. This permits the production of concentrated urine if required.
The active component of the LOH is the ascending limb. Here chloride, and hence sodium, are pumped out of the tubule into the interstitium. The ascending limb of the LOH is impermeable to water.
The descending limb of the LOH is permeable to sodium chloride and water.
The net effect is for sodium chloride to leave the ascending limb and to enter the descending limb, having first passed through the renal medullary interstitium. Some water is also lost from the descending limb.
As the tubular fluid passes through the ascending limb it becomes increasingly dilute as the sodium chloride is removed. As a result the fluid entering the distal convoluted tubule is hypotonic (150 mmol/L).
NFP is influenced by what
mostly affected by?
Afferent glomerular capillary hydrostatic pressure
Single factor most likely to determine the net filtration pressure
The net filtration pressure (NFP) is influenced by the Starling forces acting across the glomerular capillary membrane.
The glomerular hydrostatic pressures are approximately 60 mmHg at the afferent (arteriole) end and approximately 58 mmHg at the efferent (arteriole) end. Unlike most other capillary beds, the efferent end does not drain directly into a venule. The high resistance and pressure within the network of capillaries within the glomerulus aids the process of ultra filtration.
The hydrostatic pressure acting in the opposite direction is that within the Bowman’s capsule is in the order of 15 mmHg.
The glomerular capillary oncotic pressure is in the order of 21 mmHg afferent and 33 mmHg efferent end. The interstitial pressure in Bowman’s space is negligible and is not factored in.
NFP (afferent end) is calculated 60-15-21=24 mmHg
NFP (efferent end) is calculated 58-15-33=10 mmHg.
Average NFP is thought to be 17 mmHg sufficient to produce 180L/day of glomerular filtrate.
GFR= K1 x NFP
Where K1 is the filtration coefficient dependent on membrane permeability and surface area available.
Basic functional unit of kidney is
How many per kidney
what does it consisty of
how many types of nephron
what is the % split
What are the differences
How much CO received
What is RBF
& renal plasma flow
The basic functional unit of the kidney is the nephron. There are about 1.2 million nephrons in each kidney. Each nephron consists of:
A glomerulus Proximal convoluted tubule Loop of Henle Distal convoluted tubule and, A collecting duct.
There are two types of nephron in the kidneys:
Cortical (superficial) nephrons (80%) have short loops of Henle the glomerular efferent arterioles of which supply peritubular capillaries
Juxtamedullary (deep) nephrons (20%) have long loops of Henle the glomerular efferent arterioles of which supply peritubular capillaries and vasa recta.
The kidney receives 20-25% of the cardiac output at rest, which gives it a renal blood flow of 1200 ml/minute or a renal plasma plasma flow of 650 ml/minute.
