What are the functional units of the kidney and what do they consist of?
Nephrons (consisting of:)
1- Bowmans capsule (with glomerulus etc) +
2- Renal tubule
Where does filtration take place in the kidney?
The renal corpuscle (bowmans capsule + glomerulus)
What processes occur in the renal tubule?
Nutrient reabsorption
Water reabsorbtion (90% reabsorbed)
Secretion of waste products not already filtered
Where does the ureter originate from and what course does it take?
From the pelvis of each kidney, descending over the top of psoas minor and in-front of the common iliac artery, into the R/L sides of the bladder
Where does the renal artery leave the abdominal aorta?
L2
What are the 4 layers which surround each kidney?
Pararenal fat (post/ posteriolat only) Perirenal fat (around whole kidney) Renal fascia Renal capsule (fibrous)
What is the renal sinus?
Cavity within the kidney which is occupied by the renal pelvis/ renal calyx BV’s/ nerves and fat
What is the renal pelvis?
Dilation of ureter at kidney hilum
What are renal calyces (single: calyx)? What are the two types?
Chambers through which urine passes
Minor: At the apex of each pyramid
Major: Lead to renal pelvis
How does the kidney endothelium repel proteins such as albumin? How is the affected in diabetes?
Has a negative charge so repels proteins
Charge lost in diabetes so = proteinuria
What is the main function of the PCT?
Reabsorb ions and organic nutrients
Reabsorbs water
What is the main function of the loop of henle (both limbs)?
Descending limb: Reabsorbs water
Ascending limb: Reabsorbes Na+/Cl-
What is the main function of the DCT?
Secretion of ions/acids/drugs/toxins
Variable water/ion re-absorption - this is fine tuned by hormones
Where is urea re-absorbed from tubular fluid?
Collecting ducts
Where does the tubular fluid go once it has left the DCT?
Many DCT’s feed into 1 collecting duct
Collecting duct feeds to minor calyx (now as urine)
What is counter-current multipilication?
Na+/Cl-/K+ re-absorption in the ascending loop of Henle by active transport creates an osmotic gradient with passively draws out water from the descending loop of Henle
What happens to substances reabsorbed in the nephron?
Go into peritubular capillaries
These all drain eventually to the efferent arteriole
What type of epithelium lines the PCT?
Cuboidal cells with microvilli
What type of epithelium lines the Loop of Henle?
Squamous/ low cuboidal cells
What type of epithelium lines the DCT?
Cuboidal cells w/o microvilli
What type of epithelium lines the collecting ducts?
Cuboidal cells w/o microvilli
What type of epithelium lines the papillary ducts?
Columnar cells
What are the two types of nephrons?
Cortical (85%) - Stay in cortex- their peritubular capilaries drain to cortical radiate veins
Juxtamedullary (15%)- Peritubular capilaries drain to vasa recta
What are the two layers of epithelium in the renal corpuscle?
Outer: Simple squamous
Visceral: Has podocytes with filtration slits between them
What are mesangial cells?
Support cells between capillaries, they can contract to dilate or constrict vessels
What substances act on mesangial cells?
Angiotensin II, ADH, histamine
What are the two main glucose transporters in the kidney?
GLUT 1 (2Na+ to 1 glucose) - High affinity/ low capacitity
- Found in the late proximal tubule
GLUT 2 (1Na+ to 1glucose) - Low affinity/ high capacity
- Found in the early proximal tubule
What is the capacity of the glucose transporters in the kidney, what impact could this have clinically?
1.25mmol/min
So if plasma glucose is greater than 10mmol/L you will start to get glucosuria
Where do gluconeogenesis and glycolysis happen in the kidney?
Roughly 20% of bodies gluconeogenesis happens in the cortex of the kidney
Glycolysis happens in the medulla
To increase filtration rate what must happen to the afferent and efferent arterioles?
Afferent must dilate
Efferent must constrict
What is GFR?
Rate of filtration per unit time
How do you calculate GFR?
Plasma conc (x)
An increase in glomerular capillary hydostatic pressure will have what effect on GFR?
Increase it
An increase in bowmans capsule hydostatic pressure will have what effect on GFR?
Decrease it
An increase in glomerular capillary oncotic pressure will have what effect on GFR?
Decrease it
What three waste substances must be removed by the kidneys and why?
Need to be dissolved in water
Urea (from AA breakdown)
Creatinine (from creatinine phosphate in muscle)
Uric acid (from recycling nitrogen bases in RNA)
What is the anatomy of the juxtaglomerular complex?
Juxtaglomerular complex = (Epithelium of DCT near renal corpuscle - ka macula densa) + (smooth muscle cells in afferent arteriole - ka juxtaglomerular cells)
What two things are secreted by the juxtaglomerular complex?
Renin and EPO
What stimuli cause the JG complex to release renin?
Decreased BP in glomerulus
When stimulated by SNS
Low osmotic conc of tubular fluid
What is ANP?
A powerful vasodilator molecule released by the atria
It causes dilation of afferent arterioles and constriction of efferent arterioles thus increasing GFR
What is BNP?
A powerful vasodilator molecule released by the ventricles
It causes dilation of afferent arterioles and constriction of efferent arterioles thus increasing GFR
What is the function of renin?
Converts angiotensinogen (from liver) to Angiotensin I
What converted Angiotensin I to Angiotensin II?
ACE in epithelial cells
Mainly in lungs
What are the effects of angiotensin II?
SM vasoconstriction / renal water retention (Increase BP)
Pituitary releases ADH
Zona glomerulosa releases aldosterone
Increased thirst and cardiac output
How do changes in blood volume regulated GFR?
Increased blood volume = increased GFR
This promotes fluid loss
What does sympathetic stimulation do to GFR? How?
Powerfully decreases GFR
By constricting afferent arteriole
Raised urea indicates what?
Raised urea and raised creatinine indicates what?
Inc urea: Renal failure OR high protein load (starvation or exercise)
Inc urea + creatinine: Renal failure only
What can chronic raised levels of cortisol do to glucose levels?
Caused chronic hyperglycemia
lead to diabetes
What is the key feature of cushings syndrome?
Chronically elevated cortisol Central obesity (face) with limb sparing
How does cortisol affect insulin levels?
Cortisol acts to INHIBIT insulin
What is the role of carbonic anhydrase?
Converts H2O + CO2 === H+ and HCO3-
Where are carbonic anhydrase enzymes commonly found and what are the two subtypes?
Found in lung and kidney
CAII (type2)- Soluble in cytoplasm
CAIV (type4)- Extra-cellular (linked to membrane by GP1)
What is the main area of acid secretion in the nephron?
PCT
Gluatamine metabolism produces what?
HCO3- and NH3
NH3 joins H+ to make NH4+ and is secreted in PCT
What happens to the H+ and HCO3- produced by carbonic anhydrase?
H+ is secreted into tubular fluid (where it often combines to be buffered by phosphate H2PO4-)
HCO3- is often re-absorbed into blood (although this costs ATP)
Foamy urine is a sign of what?
Proteinuria
What are microabuminuria and proteinuria signs off?
Kidney damage (leaking proteins)
Why do diabetic patients sometimes experience oedema?
Due to protein loss in kidney lowering blood oncotic pressure
What do patients with diabetic nephropathy experience hyperlipidemia?
Lowered triglyceride clearance in the kidney
Lowered lipoprotein lipase activity
Why do patients with diabetes experience raised BP?
Due to a decreased GFR (renal impairment)
Why are patients with diabetic nephropathy asked to keep to a low protein diet?
So less metabolites of protein are released into the blood (toxicity)
What is the clinical definition of CKD?
End stage, advanced kidney disease
eGFR less than 60ml/min for greater than 3months
Name 5 signs of CKD:
Anorexia / pruitus / peripheral oedema / weakness / fatigue / nocturia
Which AB’s should be avoided in Px with CKD?
Penacillins/ cephalosporins
What does NICE recommend as treatment for CKD?
Start with ACEI
> Diuretics
> Dialysis
How is peritoneal dialysis conducted?
Incision made just below navel and permenant ‘tenckhoff’ catheter inserted
Dialysate fluid is pumped in, catheter is sealed, fluid left for a while then removed again (with waste)
What are the two types of peritoneal dialysis?
CAPD (continous ambulatory)- Done at home with wheelchair stand to hang bags from, 4 times daily
APD (automated PD)- Done by a machine overnight, fluid left in during day and removed next night
What is haemodialysis?
Arteriovenous fistula created in wrist/ upper arm
Two needles inserted into fistula and connected to a machine
Done 3x/week for ~4hrs at a time
What lifestyle changes must Px on haemodialysis undergo?
Limited to 1L of fluid per day (so to not overload kidney)
Px cuts down on high Na+/K+ foods
90% of pancreas transplants are of what type?
SPK (simultaneous pancreas-kidney)
What causes acidosis in CKD?
Not enough acid secretion
HCO3- is lowered as it tries to mop up H+
Px hyperventilates and pCO2 is low (resp compensation)
Why is K+ raised during acidosis?
Because excess H+ in blood is pumped into cells and swapped for K+
(Also in CKD there is less K+ excretion)
Why do patients with CKD experience a swollen face and increased body weight?
Due to increased cortisol (as less is excreted)
What is an anion gap and what does a raised anion gap indicate?
Difference between Na+/K+ and HCO3-/ Cl-
Raised anion gap can indicate metabolic acidosis
What is the NET result of each H+ leaving a tubular cell in the kidney?
A HCO3- leaves on the basolateral side into serum
Where does 90% of the bicarbonate reabsorption (and H+ secretion occur)?
Proximal convoluted tubule
How does the body remove H+ in the late distal tubules and collecting ducts?
H+ secreted by primary active transport (usually with Cl-)
What is the pH of urine and which buffer system is this closest to?
6.8
Closest to phosphate buffer system
Where does the ammonia buffer system originate from?
Glutamine is metabolised in liver to two NH4+ and two HCO3-
Why are nephrotic patients vulnerable to infection, which infections are they particually vulnerable to?
Staphylococcal and pneumococcal
Due to loss of immunoglobulins through the leaky renal filtration membranes