U Flashcards
State and be able to identify the anatomical (retroperitoneal)
position of the kidneys
posterior abdominal wall, either side of the vertebral column.
Located between the T12 and L3 vertebrae - Partially protected by ribs 11 and 12 - Hilum at L1
upper pole of each kidney opposite the twelfth thoracic vertebra
lower pole opposite the second/third lumbar vertebra
Describe the normal size of each kidney
11cm long x 6cm wide
Left kidney from T12 to L3
Right kidney from T12/L1 to L3
Describe the position of the kidneys,
Retroperitoneum, either side of vertebral column
Kidney blood supply
Renal artery enters the hilar region and usually divides to form an anterior and a posterior branch.
Then segmental artery
Interlobar
Arcuate
Interlobular
Peritubular capillaries + vasa recta
Interlobular vein
Arcuate
Interlobar
Segmental
Renal vein
IVC
Sometimes supplied by additional aberrant arteries from the superior mesenteric, suprarenal and testicular/ovarian arteries
Identify the medulla, cortex, renal pyramids and associated
structures within a human kidney
Course of the ureters
Also relationship to:
iliac and uterine vessels
ovary/vas
urethra in both males and females
males: ureter passes under ductus deferens, superior to seminal vesicles
women: ureter descends posterior to ovary and into base of broad ligament, passing under uterine artery
Describe how the ureter enters posterolateral surface of bladder
and runs obliquely through the bladder wall
Lateral to the tips of the transverse processes of the lumbar vertebrae
Divided into:
- proximal (abdominal), middle (pelvic) and distal (intramural)
Often crosses the sacrum at approximately the SI joint and descends into the pelvis.
The ischial spine shows the approximate point at which the ureter ‘kink’ towards the bladder
The ureters then run around the pelvis and enter the bladder posteriorly.
identify the anatomical position of the bladder
Describe the bladder wall composition
Describe bladder base
Describe the region of the bladder neck,
- When empty the bladder rests on the symphysis pubis
- Women – In front of vagina, uterus and rectum. Space between uterus and bladder is vesicouterine pouch.
- Men – on top of prostate. in front of rectum. Space between bladder and rectum is rectovesical pouch.
Bladder wall composed of detector muscle. Has muscular folds called rugae – contract and expand.
Lined with transitional epithelium – urothelium
Bladder base has trigone.
Trigone (triangular area) - smooth mucosa, 3 openings - Ureteric openings and internal urethral orifice.
Circularly around the bladder neck, the detrusor muscle forms the internal urethral sphincter. During bladder contraction, it contracts around the ureteric orifices to prevent vesicoureteral reflux.
Identify the anatomical position of the prostate
Identify the ultra-structure of the urethra and its muscle layers
To examine renal blood flow and GFR, clearance
Renal blood flow -mL/min
Renal plasma flow - 1-haematocrit
GFR - amount of filtrate that is produced from the blood flow, per unit time (mL/min). The amount of filtrate is determined by the product of the average filtration of each nephron in each kidney.
Dec GFR can mean dec nephrons or dec GFR within individual nephrons. ↑in GFR means that kidney function has recovered
When kidney function declines slowly, individual nephrons may hypertrophy, so actual kidney function may not fall until significant kidney damage has occurred
Clearance - volume of plasma that is cleared of a substance in a unit of time
Be able to describe how GFR and clearance are related and
calculated
GFR = 125ml/min
Renal plasma flow = 600ml/min
Filtration fraction = GFR/RPF. Usually 20%.
Renal clearance is a surrogate for GFR - ( urine conc of substance in mg/mL x flow rate of urine in ml/min ) / plasma conc of substance in mg/ml
Filtration rate of a substance = plasma conc x GFR
Excretion rate of a substance = urine conc x GFR
Process of glomerular filtration
Factors affecting GFR
Best way to measure GFR and pros and cons
Hydrostatic pressure in capillary (Pgc)
HP in Bowman’s capsule (Pbc)
Oncotic pressure diff between capillary and tubular lumen ( pi GC)
HP capillary is higher than HP bowman’s and oncotic pressure (due to albumin in capillaries) together so net filtration out of capillaries.
Age - babies have lower GFR about 20ml/min. After 30 GFR declines by 6ml/min every decade.
Pregnancy - kidney size inc so fluid vol in kidney inc so GFR inc. Reverts back to normal 6months postpartum.
Substance to measure GFR by must not be secreted into nephron, fully filtered by glomerulus, must not be reabsorbed, produced at constant rate.
1. Inulin - has all factors. Needs IV and catheter for timed urine conc measurement.
2. 51 Cr-EDTA- radioactive, injected and then plasma conc measured 2,3,4 hrs later. 10% underestimate. Used in children and kidney transplants.
3. Creatinine - dependant on protein intake, muscle mass and breakdown, sex, certain drugs eg trimethoprim. Used in pregnant woman. Collect urine over 24hr. 10-20% overestimate. Inaccurate in mild kidney disease as nephron no dec but there is nephron hypertrophy and inc secretion into tubule.
4. eGFR - estimate by putting in sex, plasma creatinine and age of patient.
Renal auto regulation. myogenic regulation and tuboglomerular feedback
Arterial smooth muscle inc and dec in wall tension
Afferent vasoconstricts to prevent transmission of inc BP to glomerular capillary.
Efferent vasoconstricts if dec BP to inc pressure
High BP/Na+
Macula densa cells of the DCT epithelium detect osmolality or the rate of movement of Na+ or Cl- movement into the cells (the higher the flow of filtrate the higher the Na+ conc in cells).
A signal is sent via the juxtaglomerular cells (triggered by an increase in NaCl conc of distal tubular fluid) ATP released, converted to adenosine, binds with A1 receptor on afferent arteriole.
Vasoconstriction therefore↓ RPF so↓GFR.
Renin synthesis inhibited.
Low BP/Na+/Effective circulating vol
Release of prostaglandins by macula densa – dec constriction of afferent arteriole. Also cortical prostaglandin synthesis by cortex, medullary interstitial cells and CD epithelial cells.
Renin is an enzyme synthesised and stored in JGA. Released by granular cells of JGA. 3 stimuli responsible for release:
•Sympathetic nerve stimulation
•↓ stretch of afferent arteriole
•Signals generated by macula densa cells in response to ↓NaCl delivery
Ang converted to Ang 1 via renin. Ang1 to Ang 2 by ACE.
Ang 2 actions:
Vasoconstriction of efferent arteriole
Release ADH
Stimulate thirst
Act on zona glomerulosa of adrenal cortex to release aldosterone. Aldosterone inc Na+ reabsorption in DCT.
Central diabetes insipidus
Impaired ADH synthesis or secretion by hypothalamus or pituitary gland - large quantity of urine.
Causes - damage to hypothalamus or p pituitary by:
Brain injury
Tumour
Sarcoidosis or TB
Aneurysm
Encephalitis or meningitis
Treat by giving ADH
Nephrogenic diabetes insipidus
Insensitivity of kidney to ADH
Causes:
Mutations in gene coding for V2 receptors, chronic pyelonephritis, polycystic kidneys, lithium
Treatment is low-salt and low-protein to reduce urine output.
SIADH
Excessive ADH release by PP, other sources or other conditions.
Signs include Dilutional hyponatremia, low plasma osmolality, higher urine osmolality, inappropriate Na+ excretion.
Causes:
CNS disorders
Malignancy
Lung disease
Drugs eg opiates
Metabolic diseases eg porphria, hyperthyroidism
The diagnosis should be considered in hyponatremic patients in the absence of hypovolemia, oedema, endocrine dysfunction, renal failure and drugs. All of which can impair water excretion.
How you produce conc or dilute urine
Countercurrent multiplication and urea recycling
1- Descending limb is permeable to water.
Osmolality inc as we descend into medulla
So always an osmotic gradient for water - moves into tubule.
2- the filtrate has lost so much water, there is now a very high
concentration of solutes. Osmolality increased to ~1200mOsm
3- As filtrate ascends, the NKCC co-transporter reabsorbs Na+, K+ and 2Cl- along the thick
ascending limb.
Osmolality decreases to ~100mOsm by top of thick ascending limb LoH
4- Vasa recta runs in the opposite direction. There is always a higher concentration of solutes in the interstitium
(compared to descending vasa recta). Solutes diffuse into vasa recta
Corticocapillary osmotic gradient
Established by
Urea recycling
Countercurrent multiplication
Maintained by
Vasa recta
Urea recycling
Purpose is to maintain hypertonicity of interstitium so water can be reabsorbed.
100% urea filtered into glomerulus
50% reabsorbed from PCT
Urea diffuses down conc gradient into descending limb of LoH near the bottom of the loop. In tubular fluid conc is now 110%.
At CD 70% of urea pumped out by UT1 transporters. These transporters can be upregulated by ADH.
Variable water permeability of collecting tubules and ducts determine urine conc
Loop of Henle
Descending is permeable to Na+ and Cl-
Ascending is impermeable to water and has NKCC co transporter in apical membrane.
Carbonic anhydrase inhibitors
acetazolamide
Acts on PCT
Weak - Na+ lost can be reabsorbed further along the nephron.
Stops H2CO3 from becoming water and CO2.
This means they cannot passively diffuse into cell and reform into bicarbonate ions and hydrogen ions.
This means less H+ out of cell so less Na+ into cell via antiporter.
So less water into cell.
Also more bicarbonate ions go into blood.
Uses
Glaucoma
Side effects
Metabolic acidosis
Renal stones
K+ wasting
CNS effects - parathesia + drowsiness
Osmotic diuretics
Mannitol - IV
In the blood, then fully filtered in glomerulus, so in lumen
Water diuresis - is a sugar so pulls water into lumen via osmotic gradient
Uses
Acute renal failure due to shock - inc renal blood flow
Acute drug poisoning- eliminates drugs reabsorbed into tubule
Dec intracranial and intraocular pressure
Side effects
Expands extracellular fluid vol initially- Not used in heart failure and pulmonary oedema
Dec blood viscosity, inhibits renin release
Can cause hyponatraemia due to sodium following water which will cause headache, nausea, vomiting
Hypernatraemia when excessive use due to dehydration
Loop diuretics
Furosemide
Act on ascending loop of Henle
Most potent
Mechanism:
Inhibit Na-K-2Cl transporter in the thick ascending limb of loop of Henle → excretion of sodium, potassium, and chloride → water excretion
Uses
Severe oedema
Oliguric AKI
Hypercalcemia (This is because more potassium goes out through leaky channels so membrane of cell is more positive so repels magnesium and calcium ions. This means more is excreted)
Hyperkalaemia
Toxicity of Br, F & I
Side effects
- Hypovolemia
- Hyponatraemia
- Hypokalaemia
- Hypomagnesaemia
- Hypocalcaemia
- Metabolic alkalosis (Loss of lot of water means inc conc of bicarbonate ions so metabolic alkalosis)
- Postural hypotension
Thiazide and like
Bendroflumethiazide, Indapamide
1st line anti hypertensive
Acts on DCT
Mechanism:
Inhibit sodium-chloride symporters
- ↑ urinary NaCl excretion
- ↑ urinary K excretion (in CD high conc of Na. This means more Na goes into CD cells. This means lumen of CD has a more neg charge than cell. This means K+ and H+ will go into lumen down charge gradient)
- ↑ urinary magnesium excretion
- ↑ calcium reabsorption (Inc calcium reabsorption as less sodium in cell so more sodium coming in via Na+/Ca2+ exchanger so more Ca2+ leaves blood)
Uses
- Hypercalciuria
- Osteoporosis
Essential hypertension
- Mild heart failure
- Calcium nephrolithiasis due to hypercalciuria
- Nephrogenic diabetes insipidus polyuria
Potassium sparing and aldosterone antagonist
Spironolactone (competitive antagonist) and Amiloride
Act on CD
Block aldosterone receptors → decrease the synthesis of epithelial sodium channels (ENaC) and hydrogen pumps → increase sodium excretion, and decrease potassium and hydrogen excretion
Less K+ lost as blocks the pump so less K+ into cell from blood
Block ROMK channels
Block ENAC channel
Can be given with loop diuretic as that makes patients hypokalaemic
Explain the renal mechanisms for the regulation of extracellular fluid volume and
composition
Renin-angiotensin-aldosterone system
Prostaglandins (synthesis in Cortex - arterioles and glomeruli, Medullary interstitial cells , Collecting duct epithelial cells)
ANP
- Produced by cardiac atrial cells in response to an increase in ECF volume
- Inhibit Na+/K+ ATPase and close Na+ channels of the collecting ducts and DCT,
reducing Na+ reabsorption.
- Vasodilate afferent arterioles, thereby increasing GFR
- Inhibit aldosterone secretion
- Inhibit ADH release
- Decrease renin release
Starlings forces in the PCT
- Changes in body fluid volume alter plasma hydrostatic
and oncotic pressure e.g. ↑NaCl intake mirrored by
↑ECF volume
- This ↑hydrostatic pressure and ↓oncotic pressure, so NaCl and water reabsorption by the PCT decreases
When renal artery BP increases
- Reduced number of Na-H antiporter in PCT
- Causes reduction in sodium reabsorption in PCT
(Glomerular tubular balance) - Leads to a reduction in water reabsorption in PCT
- Describe, in principle, the management of electrolyte and body fluid disturbances - To examine how the body regulates body fluid osmolality in terms of responses to water
deprivation and drinking
Sensors - Hypothalamic Osmoreceptors
In the OVLT (Organum Vasculosum of the
Lamina Terminalis)
Fenestrated leaky endothelium exposed to systemic circulation (on plasma side of Blood Brain Barrier)
Efferent pathways - 1)ADH 2) Thirst
ADH detailed
binds to V2 receptors on the basal membrane
- G-protein coupled receptors, when activated, cause
fusion of inactive aquaporin 2 vesicles with the luminal membrane
- Review how hormones, sympathetic nerves and Starling forces regulate NaCl
reabsorption
Hormones - prostaglandins
Starling forces - changes oncotic and hydrostatic pressure so change in movement of fluid from PCT into peritubular capillaries.
Sympathetic - dec BP sensed by Baroreceptors which inc cardiac output and peripheral resistance.
- Review how RAAS regulates sodium ion uptake in response to changes in blood
pressure
- Explain the kidney’s response to hypotension
Organs inadequately perfused
Inadequate delivery of O2 and nutrients to cells result in a hypoxic state leading to anaerobic metabolism and inefficient clearance of metabolites.
Can lead to acute tubular necrosis (ATN) in kidney.
Hypovolemia and mild shock cause; tiredness, dizziness and a feeling of thirst.
Vasodilation occurs in the vital organs to maintain blood supply.
More prostaglandins secreted in kidneys
– maintains adequate blood flow GFR
- The loss of large amounts of fluid has 2 major consequences
- Volume depletion (decreases tissue perfusion)
- Electrolyte and acid-base disturbances
- Describe hypertensive renal disease
Renal autoregulation maintains
despite variations in systolic BP.
Hypertensive changes seen in the kidney include:
- Arteriosclerosis of the major renal arteries
- Hyalinization of the small vessels with intimal
thickening - This can lead to chronic renal damage and a
reduction in the size of the kidneys
Secondary renal causes:
- Impaired Na+ and water excretion, increasing blood volume
- Stimulation of renin release
- Renal artery stenosis also causes reduced perfusion of the kidney and therefore excessive activation of the RAAS
- Understand how fluid overload occurs
Typically due to:
- Kidney retention of sodium and water
- Reduced effective arterial volume e.g. CCF
- Excessive sodium or fluid intake
- Cirrhosis
- Hyperaldosteronism
- Understand how the kidney can cause hypertension
Osmotic v haemodynamic
Look at graph on slide
Changes in BP have an effect on the response to changes in osmolarity
- ↓ in BP
The set point is shifted to lower
and the slope of the relationship is steeper - ↑ in BP
- The set point is shifted higher and the slope dec
Volume is more important than osmolarity if volume crashes
To explore the clinical signs and symptoms of acute and chronic hyponatraemia
Osmolality
Hyperosmotic- eg mannitol, hyperglycaemic
Hypo - fluid depleted - high urinary Na+ conc:
Diuretics
Renal failure
Cerebral salt- wasting
Mineralocorticoid deficiency
SIADH
Glucocorticoid deficiency
Hypothyroidism
If low Na+ in urine:
Extra-renal loss - GI losses, excessive sweating, ascites/peritonitis, burns
If oedematous instead of depleted:
Low U Na+ = renal failure
High = nephrotic syndrome, cirrhosis, cardiac failure
True Na+ loss:
D&V -
Diuretics/renal failure - Peritonitis
- Burns/CF
Liver disease - Tumours (Small cell lung CA)
Medications
- Thiazide diuretics
- Selective serotonin reuptake inhibitors (SSRIs)
- Proton pump inhibitors
- Angiotensin-converting enzyme (ACE) inhibitors
- Loop diuretics
Symptoms:
Neurological: agitation, nausea,
focal neurology, coma
Treatment:
Fluid restriction
Infusion of hypertonic saline + furosemide can be used in symptomatic patients
