10 Flashcards
Are the kidneys intraperitoneal or retroperitoneal organs?
Retroperitoneal
Which surface of the kidneys are covered with peritoneum?
Anterior surface
Which muscles lie posterior to the kidneys and offer protection?
Psoas major
Quadratus lumborum
Where in the abdomen are the kidneys located?
Posterior abdomen
Upper L and R quadrants
What does ‘retroperitoneal’ mean?
Behind the peritoneum.
Which vertebral levels do the kidneys level with?
T12 to L3
Which kidney is often situated slightly lower and why?
Right kidney
Due to liver
Where to the adrenal glands sit?
- Immediately superiorly to the kidneys
- Within the renal fascia
The kidneys are encased in complex layers of fascia and fat.
How are they arranged from deep to superficial?
Renal capsule – Tough fibrous capsule.
Perirenal (or perinephric) fat – Collection of extraperitoneal fat.
Renal (Gerota’s) fascia – Encloses the kidneys and the suprarenal glands.
Pararenal (or paranephric) fat – Mainly located on the posterolateral aspect of the kidney.
Define ‘parenchyma’
Functional tissue of an organ.
Distinguished from the connective and supporting tissue.
Which 2 main areas is the renal parenchyma divided into?
– Outer cortex
– Inner medulla
The cortex extends into the medulla, dividing it into triangular shapes – these are known as renal pyramids.
What is the apex of the renal pyramid called?
Renal papilla
What is each renal papilla associated with?
– Minor calyx
– Which collects urine from the pyramids
What merges to form a major calyx?
Several minor calyces.
Urine passess through the major calices into what?
Renal pelvis
Describe the structure of the renal pelvis.
– Flattened
– Funnel-shaped
Via which structure does renal vessels and ureter enter/exit the kidney?
Renal hilum
What does the left kidney lie posterior to?
– Adrenal gland – Spleen – Stomach – Pancreas – L colic flexure – Jejunum
What does the left kidney lie anterior to?
– Diaphragm
– Ribs: 11th, 12th
– Muscles: Psoas major, Quadratus lumborum, Transversus abdominis.
– Nerves: Subcostal, Iliohypogastric, Ilioinguinal.
What does the right kidney lie posterior to?
– Suprarenal gland
– Liver
– Duodenum
– R colic flexure
What does the right kidney lie anterior to?
– Diaphragm
– 12th rib
– Muscles: Psoas major, Quadratus lumborum, Transversus abdominis.
– Nerves: Subcostal, Iliohypogastric, Ilioinguinal.
Where does the renal arteries originate from?
Abdominal aorta
Immediately distal (below) to the origin of the superior mesenteric A.
Where does the abdominal aorta lie relative to the midline?
What significance does this have in the context of the renal arteries?
Slightly L of the midline.
Thus, the R renal A. is longer and crosses the vena cava posteriorly.
What happens once the renal arteries enter the kidneys via the renal hilum?
They divide into segmental branches.
Then they further divide to supply the renal parenchyma.
What does the segmental arteries of the kidneys divide to form?
Interlobar arteries
They are situated on either side of every renal pyramid.
Describe the divisions that occur to the renal artery when it enters the kidney via the renal hilum.
- Segmental A.
- Interlobar A.
- Arcuate A.
At 90 degrees to arcuate arteries, interlobular arteries arise
- Interlobular A.
Interlobular arteries pass through the cortex and divide 1 last time into:
- Afferent arterioles
What does the afferent arterioles form?
A capillary network, the glomerulus, where filtration takes place.
What is the peritubular network?
The is the formation of the efferent arterioles in the outer 2/3 of the cortex.
In the renal system, peritubular capillaries are tiny blood vessels, supplied by the efferent arteriole, that travel alongside nephrons allowing reabsorption and secretion between blood and the inner lumen of the nephron.
Which arteries supply the inner 1/3 of the cortex and medulla?
Vasa recta
Relative to the renal arteries, where do the renal veins lie in the renal hilum?
Anteriorly to renal arteries.
Where does the renal veins empty into?
IVC
Which renal vein is longer and why?
Left because the vena cava lies slightly to the right of the midline.
Which lies more anteriorly: renal veins or renal arteries?
Veins
Which kidney is higher?
Left kidney (T12-L3)
At which vertebral level does the transpyloric plane lie?
L1
Where does the transpyloric plane cut the L and R kidneys?
Left - hilum
Right - superior pole
Where does lymph from the kidney drain into?
The lateral aortic nodes
What is a pelvic kidney?
Embryologically, the kidneys develop in the pelvis, and ascend into the abdomen. Occasionally, one of the kidneys can fail to ascend, and remains in the pelvis, at the level of the common iliac artery.
What is a horseshoe kidney?
A horseshoe kidney (a.k.a a cake kidney or fused kidney) is where the 2 developing kidneys fuse into a single horseshoe-shaped structure.
This occurs if the kidneys become too close together during their ascent from the pelvis to the abdomen – they become fused and consequently ‘stuck’ underneath the inferior mesenteric artery.
This type of kidney is still drained by two ureters, and is usually asymptomatic, although it can be prone to obstruction.
Knowing the length of a kidney helps when interpreting any changes in size on radiographs.
Approximately how many vertebral levels does a kidney extend over?
3
Which structure encloses the kidneys and suprarenal glands?
Renal fascia
The renal vessels and ureter enter and exit the kidney via which structure?
Renal hilum
Which artery suspends the ascent of a horseshoe kidney?
Inferior mesenteric A.
From anterior to posterior, which structures lie in the renal hilum?
- Vein
- Artery
- Ureter
What is renal cell carcinoma strongly correlated with?
Smoking
Describe renal cell carcinoma.
- Linked to smoking.
- Metastasizes early.
- Spreads to other areas in body particularly lungs.
- Lungs mets appear like a cannonball.
- Poor chemotherapy response.
- Is the most common histology of kidney tumours.
- Risk highest in elderly men and with a smoking history.
- Presents w/ abdominal pain, a mass, haematuria.
- Paraneoplastic effects: EPO (over excreted from kidney), fever.
What is the renal medulla responsible for?
Generating very high tonicity that allows water reabsorption.
The medulla splits into many pyramids which all drain into papillae.
What is a renal pyramid?
Area where all collecting ducts drain into 1 papilla.
What is a papillae?
Where the collecting ducts of a pyramid drain into a minor calyx.
Several papillae drain into a minor calyx.
How many minor calyces are there?
7-13
Where do minor calyces drain into?
Major calyces which there are 2-3 of.
Where do major calyces drain into?
Renal pelvis which connects to the ureter
Describe the branching of the renal arteries once they enter the kidneys.
- Renal A. (branches at L1)
- Segmental A.
- Lobar A.
- Interlobar A.
- Arcuate A.
- Interlobular A.
- Afferent arteriole
- Glomerular capillaries
- Efferent arteriole
- Peritubular capillaries
Which plane does arcuate vessels run in?
The cortico-medullary plane.
Which wall does the ureters run along?
Posterior abdominal wall
Which surface do the ureters approach the bladder from?
Posterior surface
Which muscle do the ureters follow?
Psoas major
In females where do the ureters descend relative to the cervix?
Lateral
Where do the ureters narrow?
Pelvi-ureteric junction
Pelvic brim
Uretero-vesical junction
Describe the path of descent of the ureters.
Inferiorly along path of psoas major to pelvic brim where:
- Pass anterior to bifurcation of common iliac A.
- Anterior to sacroiliac joint
What passes anterior to ureters?
- Gonadal A. - ovarian and testicular arteries
- Colic A.
What passes posterior to ureters?
- Vas deferens
- Uterine A.
Which arteries supply the ureters?
- Renal A.
- Gonadal A. - testicular/ovarian
- Superior and inferior vesical A.
Abdominal: Renal artery and testicular/ovarian artery.
Pelvic: Superior and inferior vesical arteries.
Describe the microanatomy of the ureter.
From the lumen (deep) to superficial:
- Transitional epithelium
- Subepithelial connective tissue
- Inner circular smooth muscle
- Outer longitudinal muscle
- Fibrous tissue
Why is transitional epithelium of the ureters functionally relevant?
Can convert from cuboidal epi to squamous epi.
- Can allow dilation in the lumen wo/ sig increase in luminal pressure.
Whole urinary tract lined by this transitional epithelium.
What is the function of the inner circular and outer longitudinal muscles of the ureter?
Allows forward flow of urine (peristalsis) towards the bladder
Describe the bladder anatomy.
- Fundus is superior
- Apex lies anteriorly
- Ureters open on the inferior posterior surface
- Between ureteric orifices + urethral orifices form a triangular area (trigone)
- Muscles of bladder = detrusor muscle.
- Detrusor allows pressure in bladder to rise greater than pressure in the internal urethral sphincter –> promotes urination
- Lined by transitional epithelium w/ rugae (for greater urine capacity wo/ generating bladder pressure)
What are most bladder malignancies?
Transitional cell carcinomas
What is the muscle of the bladder?
Detrusor muscle
What is the function of the detrusor?
Allows pressure in bladder to rise greater than pressure in the internal urethral sphincter –> promotes urination.
What is the trigone?
Ureteric orifices + urethral orifices forms a triangular area (trigone) - Flat area of mucosa
Where is the internal urethral sphincter?
At bladder neck
What is the internal urethral sphincter an extension of?
Detrusor
What are the 2 types of capillaries in the kidney and what do they supply?
- Peritubular - supplies PCT DCT
- Vasa recta - supplies loop of Henle therefore go into the medulla
What are the 2 types of nephrons?
Cortical nephrons
Juxtamedullary nephrons - go right into medulla
What are the 3 components of the glomerulus?
- Epithelium with podocytes - slit pores between them
- Negatively charged basement membrane
- Capillary endothelium with fenestration
Which cells make up the juxtaglomerular apparatus and their functions?
- Granular (juxtaglomerular) cells - produce renin
- Macula densa cells - detect NaCl and release renin
- Extraglomerular mesangial cells - smooth muscle and thought to be associated with immune system
Macula densa are found where the thick ascending limb of LoH meets DCT
Where are macula densa cells found?
In the kidney, the macula densa is an area of closely packed specialized cells lining the wall of the distal tubule, at the point where the thick ascending limb meets the distal convoluted tubule.
What are the filtration pressures in the kidney and which way are they acting?
- Hydrostatic pressure of the capillaries - approx 55mmHg (out of capillaries)
- Hydrostatic pressure of bowman’s capsule - approx 15mmHg (into capillaries)
- Oncotic pressure of the bowman’s capsule - 30mmHg (into capillaries)
If you constrict the afferent arteriole, what happens to GFR?
It decreases
If you dilate the efferent arteriole, what happens to GFR?
It decreases
If you dilate the afferent arteriole, what happens to GFR?
It increases
If you constrict the efferent arteriole, what happens to GFR?
It increases
What occurs in the myogenic mechanism of autoregulation if blood pressure is too high?
Increased stretch in afferent arterioles (which increases NFP and GFR) –> afferent arteriolar vasoconstriction –> decreased glomerular BP –> decreased NFP and decreased GFR
Themyogenic mechanismis howarteriesandarteriolesreact to an increase or decrease ofblood pressureto keep the blood flow within theblood vesselconstant.
The smoothmuscleof the blood vessels reacts to the stretching of the muscle by opening ion channels, which cause the muscle todepolarise leading to muscle contraction. This significantly reduces the volume of blood able to pass through thelumen, which reduces blood flow through the blood vessel. Alternatively when the smooth muscle in the blood vessel relaxes, the ion channels close, resulting invasodilationof the blood vessel; this increases the rate of flow through the lumen.
This system is especially significant in thekidneys, where the GFR is particularly sensitive to changes in blood pressure. However, with the aid of the myogenic mechanism, the glomerular filtration rate remains very insensitive to changes in human blood pressure.
What occurs in the tubuloglomerular feedback mechanism of autoregulation, if blood pressure is too high?
Increased GFR = increased blood flow = increased NaCl detection by macula densa cells = they secrete vasoconstrictor = increased arteriolar vasoconstriction = decreased glomerular BP = decreased NFP andGFR
In the physiology of the kidney, tubuloglomerular feedback (TGF) is a feedback system inside the kidneys.
Within each nephron, information from the renal tubules (a downstream area of the tubular fluid) is signaled to the glomerulus (an upstream area).
Tubuloglomerular feedback is one of several mechanisms the kidney uses to regulate glomerular filtration rate (GFR). It involves the concept of purinergic signaling, in which an increased distal tubular sodium chloride concentration causes a basolateral release of adenosine from the macula densa cells. This initiates a cascade of events that ultimately brings GFR to an appropriate level.
What are the effects of angiotensin II?
- Aldosterone secretion
- Vasoconstriction
Upper urinary tract symptoms
Pyelonephritis:
- Loin pain
- Nausea
- Fever
- Rigors
- Leucocytosis
What are cystatin C based equation?
It is a protein secreted by most body cells which is freely filtered.
After filtration it is mostly reabsorbed and there is only a small amount excreted in the urine.
If the levels are higher in the urine, glomerular filtration has calcined.
Independent of weight, height, muscle mass, age + gender.
What are the problems with using creatinine clearance to estimate clearance?
- Affected by muscle mass
- Affected by certain drugs e.g. trimethoprim
What are obstructive voiding symptoms?
- Hesitancy
- Delay in initiating micturition
- Weak urinary stream
- Straining to void
- Incomplete emptying
- Terminal dribbling
What are storage symptoms?
- Nocturia
- Urgency
- Incontinence
- Bladder pain
- Dysuria
What would air in the urine suggest?
Vesico-colic fistula
Which electrolyte will rise with kidney injury?
Potassium
Nephrotic syndrome signs.
- Proteinuria ++++
- Frothy urine
- Hypoalbuminaemia
- Oedema: around ankles and face
- Hyperlipidaemia (secondary)
Where is the main site for EPO production?
Kidneys
So patients with kidney injury may be anaemic
What happens to bicarbonate levels in kidney injury?
They fall because kidneys cannot generate new bicarbonate and excrete hydrogen as efficently
What happens to calcium and phosphate in a kidney injury?
- Increase in phosphate levels (which causes…)
- Decrease in calcium
Normal working kidneys remove extra phosphorus in blood.
- In chronic kidney disease (CKD), kidneys cannot remove phosphorus very well.
- Extra phosphorus causes body changes that pull calcium out of bones, making them weak.
- High phosphorus levels stimulate the release of parathyroid hormone (PTH)
- High PTH result in a low calcium level in bone and high levels in the blood because the function of PTH to increase blood calcium levels
- Calcium binds with phosphate and is deposited in the tissue
Nephritic syndrome signs
- Haematuria +++
- Proteinuria ++
- Hypertension
- Low urine volume - less than 300ml/day
- Oedema may be present but not as severe as nephrotic
Alport syndrome
- Nephritic
- Caused by mutations in genes encoding glomerular basement membrane proteins
IgA nephropathy
- Nephritic
- Abnormality of IgA production and clearance
- Deposition of IgA in mesangium
Post streptococcal glomerulonephritis
- Nephritic
- Streptococcal antigens trapped in glomerular basement membrane during infection
What is nephritic syndrome?
Inflammatory reaction which seriously damages capillary walls, permitting blood to pass into the urine and reduces GFR
Describe minimal change disease?
- Glomerulus look normal under a microscope but have diffuse effacement of podocytes under electron microscope
- T cell derived
- Basement membrane less negative
What is focal segmental glomerulonephrosis?
- Sclerosis affecting some, but not all glomeruli (focal)
- Involves only segments of affected glomerulus (segmental)
- Injury to podocytes initiating events
- Deposition of hyaline masses
- IgM and complement commonly seen in lesion
What is the paracellular route?
Between tight junctions
Which side is the apical membrane?
Lumen side
Which side the basolateral side?
Capillary side
Describe primary active transport.
- On basolateral surface
- Na+/K+ ATPase pumps 3Na+ out of PCT cell and 2K+ into cell to create concentration gradient
Describe secondary active transport
- On apical surface
- Sodium gradient created by primary active transport
- Amino acids and glucose facilitated with sodium
How much sodium is reabsorbed in the PCT?n
65%
Why do you get glucose in the urine and polyuria with diabetes mellitus?
Transport maximum of glucose is breached so you get glucose in the urine.
Glucose is an osmotic diuretic so with more glucose in the urine, there is more water excretion thus polyuria.
What secretions are there into the proximal tubule?
Organic acids - penicillins, cephalosporins, bile salts, urate etc.
Organic cations - creatinine
By which route are chloride ions absorbed?
Paracellular
Between tight junctions.
What is the thin descending limb and thin ascending limb of the loop of Henle permeable to?
(Thin) descending:
- Low permeability to ions and urea
- Highly permeable to water
Thin ascending:
- Impermeable to water
- Permeable to ions
Which nerve is firing if you are holding in urine?
Pudendal as it is under voluntary control
It’s on the external urethral sphincter
Which receptors would you find on the external urethral sphincter?
Nicotinic receptors.
Respond to acetylcholine from pudendal nerve - somatic nervous system.
Which receptors would you find on the internal sphincter?
Alpha-1
Respond to NA from hypogastric nerve - sympathetic nervous system.
Which receptors would you find on the bladder?
M3 - respond to ACh from pelvic nerve - parasympathetic –> parasympathetic detrusor contraction.
B3 - respond to NA from hypogastric nerve - sympathetic –> relaxation of the detrusor smooth muscle of the urinary bladder and increases bladder capacity.
The bladder has mainly M1, M2 (80%) and M3 (20%) cholinergic receptor types, but only M3 cholinergic receptors are responsible for the parasympathetic detrusor contraction.
α-receptors are located in the trigonum and in the urethra, rarely in detrusor muscle.
- α1-Receptors are common in men
- α2-receptors are common in women
- α1-receptors are classified into 3 subtypes (A, B and D), in the urinary bladder and urethra α1A-receptors prevail.
- The adrenergic stimulation of α1A-receptors leads to an increase of bladder closure.
Describe the thin ascending loop of Henle.
- Impermeable to water
- Permeable to ions that cross by diffusion
Describe the thick ascending loop of Henle.
- Impermeable to water
- Na+ Cl- actively pumped out
What is the relationship between time of half life and steady state?
The time to reach steady state is defined by the elimination half-life of the drug.
After 1 half-life, you will have reached 50% of steady state.
After 2 half-lives (75% of steady state)
After 3 half-lives (87.5% of steady state)
After 5 half-lives (97% of steady state achieved)
What happens to ionised drugs in the kidney?
What happens to lipid soluble drugs?
Ionised drugs: stay in the tubule and are excreted in urine
Lipid soluble drugs: are almost completely reabsorbed
What is the physiology of normal micturition?
A full bladder causes stretching of the detrusor muscle which is detected by the pelvic nerve (sensory, afferent) which increases the rate of firing of nerve impulses to the sacral region of the spinal cord.
This then bypasses the thoracolumbar region to go to the pontine micturition centre.
What happens to lipid soluble drugs?
They are almost completely reabsorbed
What is the steady state of a drug?
Drug is at peak level in system
Around 4 doses needed for drug to attain a steady state
What do principal cells of the kidneys respond to and secrete?
Principal cells are the main Na+ reabsorbing cells and the site of action of aldosterone, K+-sparing diuretics, and spironolactone.
Respond to ADH and Aldosterone - secrete K+.
The principal cell mediates the collecting ducts influence on Na+ and K+ balance via sodium channels and potassium channels located on the cell’s apical membrane.
Aldosterone determines expression of sodium channels (especially the ENaC). Increases in aldosterone increase expression of luminal sodium channels.
Aldosterone also increases the number of Na⁺/K⁺-ATPase pumps. That allow increased sodium reabsorption and potassium secretion.
Vasopressin (ADH) determines the expression of aquaporin channels that provide a physical pathway for water to pass through the principal cells.
Together, aldosterone and vasopressin let the principal cell control the quantity of water that is reabsorbed.
What happens to acidic drugs in alkaline urine?
More readily ionised so are more soluble in water
What happens to alkaline drugs in acidic urine?
More readily ionised so are more soluble in water
What do intercalated cells secrete?
H+
Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis
What happens when the pontine micturition centre is activated?
- Inhibition of hypogastric sympathetic nerve = no relaxation of detrusor muscle (B3) therefore contraction occurs
- Inhibition of hypogastric sympathetic nerve = no function of internal sphincter (alpha-1) therefore it relaxes
- Inhibition of pudendal nerve = relaxation of external sphincter
What is classed as a complicated UTI?
Involves:
- Children
- Catheters
- Or is Haematogenous (originating in or carried by the blood rather than ascending up the urinary system)
What are the route of infection of a UTI?
- Ascending
- Haematogenous: through bloodstream, through kidneys descending down
What is continuous incontinence?
Continuous loss of urine at all times
What is functional incontinence?
Incontinence due to cognitive impairment
Causes of functional incontinence: confusion, dementia, poor eyesight, impaired mobility or dexterity or unwillingness to use the toilet due to depression or anxiety.
Functional incontinence is more common in elderly people as many of the causes are associated with conditions that affect people as they age. For example, a person with Alzheimer’s disease may not plan well enough to reach a bathroom in time or may not remember how to get to the bathroom.
What are the main causes of voiding difficulties?
- Increased outflow resistance at bladder neck
- Urethral stricture
- Detrusor muscle failure
What is the pathology of BPH?
Hyperplasia of both the lateral and median lobes leading to compression and urethra and therefore bladder obstruction. Within the prostate there are solid nodules of fibromuscular material.
What is urge incontinence?
When you have a sudden urge to urinate.
In urge incontinence, the bladder contracts when it shouldn’t, causing some urine to leak through the sphincter muscles holding the bladder closed.
What is stress incontinence?
Involuntary leakage of small amounts of urine due to high abdominal pressure (e.g. coughing, laughing, sneezing etc.)
What is overflow incontinence?
Involuntary leakage when the bladder is full
What does nosocomial mean?
Disease originating in hospital
Who gets UTIs?
- Infants
- Early childhood - male and female same rate at this point
- Late teens/early 20’s female
- Elderly men
Describe metanephros.
Develops in sacral region of embryo
About 5 weeks of gestation
Form final adult kidneys
Becomes functional in latter part of pregnancy
What is the ureteric bud?
Outgrowth of mesonephric duct
Eventually dilates and splits to form the renal pelvis, calyces and collecting tubules
What feature of E. Coli allows it to survive in the bladder?
Type I fimbriae which bind to mannose residues on host cells
Type P fimbriae can bind to kidney cells as well as bladder cells
Main cause of community acquired UTI?
E. Coli
Describe mesonephros.
Develops in lumbar region of embryo
4th-5th week of gestation
Consists of excretory tubules with their own collecting ducts - mesonephric ducts
Mesonephric ducts drain into nephritic duct
Main cause of hospital acquired UTI?
E. Coli
Other than E coli, what are other causes of UTI?
- Mycobacterium tuberculosis
- Adenovirus
- JC and BK virus
- Schistosoma (parasitic flatworm)
What are some host defences against UTIs?
- Urine flow
- Urine pH, osmolality
- Secretory factors such as secretory IgA and lactoferrin
- Mucosal defences
- Macrophages
Bacterial virulence factors of uropathogenic E. Coli.
- Capsule
- Resists phagocytosis
- K antigen - can induce immune response
- Type I fimbriae - cause cystitis bind to mannose residues
- Type P fimbriae - can cause pyelonephritis and cystitis
Bacterial virulence factors of Proteus species.
- Gr-
- Produces urease
- Increases urine pH
Three species (P. vulgaris, P. mirabilis, and P. penneri) are opportunistic human pathogens.
P. mirabilis, once attached to the urinary tract, infects the kidney more commonly than E. coli. P. mirabilis is often found as a free-living organism in soil and water.
P mirabilis - associated with formation of magnesium ammonium phosphate (struvite) stones
Describe pronephros.
Develops in cervical region embryo
4th week of gestation
Non-functional and regresses soon after formation leaving behind the NEPHRITIC DUCT
What are the 3 embryological stages of the kidney?
- Pronephros
- Mesonephros
- Metanephros
Where does the metanephros originally rely on their blood supply from?
Branches of aorta
Later on, kidney ascends into lumbar region and its primary blood supply is from renal arteries
How might a UTI present in infants?
Poor feeding and failure to thrive
Which results on urinalysis suggest UTI?
- +ve leucocyte esterase
- +ve nitrites
How can we prevent UTIs in people who need catheters?
- Not catheterising
- Limit duration of catheterisation
- Aseptic insertion
- Closed drainage system - catheter into sealed bag
- Ag++ bonded catheters
What is urethral syndrome and its possible causes?
Symptoms of lower UTI without bacteria
STI could cause, non-infective inflammation
Which bacteria is Nitrofurantoin not effective against?
Proteus species
Risk factors for UTI in children?
- Poor urine flow
- Constipation
- Spinal lesion
What is a buffer?
When acid or base is added to it, minimises change in pH
What does the Guthrie test test for?
PKU
Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated, PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin.
What type of carcinoma is penile cancer?
Squamous cell carcinoma
What are risk factors for penile cancer?
- Smoking
- HPV
- Poor hygiene/smegma
What type of carcinoma is prostate cancer?
Adenocarcinoma
What is the staging for bladder cancer?
Tis: This stage is carcinoma in situ (CIS) or a “flat tumor.” This means that the cancer is only found on or near the surface of the bladder. The doctor may also call it non-muscle-invasive bladder cancer, superficial bladder cancer, or noninvasive flat carcinoma. This type of bladder cancer often comes back after treatment, usually as another noninvasive cancer in the bladder.
T1: The tumor has spread to the connective tissue (called the lamina propria) that separates the lining of the bladder from the muscles beneath, but it does not involve the bladder wall muscle.
T2: The tumor has spread to the muscle of the bladder wall.
T2a: The tumor has spread to the inner half of the muscle of the bladder wall, which may be called the superficial muscle.
T2b: The tumor has spread to the deep muscle of the bladder (the outer half of the muscle).
T3: The tumor has grown into the perivesical tissue (the fatty tissue that surrounds the bladder).
T3a: The tumor has grown into the perivesical tissue, as seen through a microscope.
T3b: The tumor has grown into the perivesical tissue macroscopically. This means that the tumor(s) is large enough to be seen during imaging tests or to be seen or felt by the doctor.
T4: The tumor has spread to any of the following: the abdominal wall, the pelvic wall, a man’s prostate or seminal vesicle (the tubes that carry semen), or a woman’s uterus or vagina.
T4a: The tumor has spread to the prostate, seminal vesicles, uterus, or vagina.
T4b: The tumor has spread to the pelvic wall or the abdominal wall.
N0 (N plus zero): The cancer has not spread to the regional lymph nodes.
N1: The cancer has spread to a single regional lymph node in the pelvis.
N2: The cancer has spread to 2 or more regional lymph nodes in the pelvis.
N3: The cancer has spread to the common iliac lymph nodes, which are located behind the major arteries in the pelvis, above the bladder.
M0 (M plus zero): The disease has not metastasized.
M1: There is distant metastasis.
M1a: The cancer has spread only to lymph nodes outside of the pelvis.
M1b: The cancer has spread other parts of the body.
What are the types of bladder/ureter/renal pelvis cancer?
- Transitional cell
- Squamous cell carcinoma
- Adenocarcinoma
What is the henderson-hasselbach equation?
pH = pKa + log (HCO3-/H2CO3)
How does haemoglobin act as a buffer?
NH3+ - donates H+ ion if there is a lot of base added.
COO- - accepts H+ ion if there is a lot of acid added
What are the 2 phosphate salts that act as buffers and how?
Sodium dihydrogen phosphate - acid phosphate
Disodium dihydrogen phosphate - alkaline phosphate
Alkaline phosphate converted to acid phosphate which generates Na+ and binds to H+ in the lumen, generating HCO3- for plasma
How is ammonium generated in proximal tubule lumen?
Deamination of glutamine produces NH4+ and HCO3- in the proximal tubular cell
When CO2 increases, what happens to pH?
CO2 increases = [H+] increase = DECREASED PH
How do the kidneys prevent acidosis?
- Reabsorption of HCO3-
- Excretion of H+
What happens to the ammonium in the proximal tubule?
Secreted into the lumen
Why does acidosis increase NH4+ excretion?
- Acidosis stimulates the enzymes that deaminate glutamate = increase in ammonium
- Increased H+ secretion results in NH3 production, which results in increased NH4+ in the collecting tubules. The conversion of NH3 to NH4+ maintains a gradient for NH3 secretion so excess NH4+ is removed from the medulla
What pH is acidaemia?
Less than 7.35
What are some causes of respiratory acidosis?
- COPD
- Obstruction of airway
- Severe asthma
- Morphine, barbiturates
What pH is alkalemia?
More than 7.45
What would the pH, PCO2 and HCO3- be in respiratory alkalosis?
- pH = high
- PCO2 = low
Kidneys start to excrete HCO3 and retain H+ to lower pH
What are the causes of metabolic alkalosis?
- Loss of acid e.g. vomiting and diarrhoea
- Ingestion of alkali e.g. antacid
- Depleted ECF
What is bladder extrophy?
Where the bladder and cloaca haven’t fused properly so bladder is open on the abdomen
What is the compensatory mechanism involved in respiratory alkalosis?
- As there is too much CO2 being removed, this causes [H+] levels to fall and therefore increase in pH and decreased [HCO3-]
- Reduce H+ secretion
- Decreased HCO3- reabsorption
What would the pH, PCO2 and HCO3- be in metabolic alkalosis?
- pH = high
- PCO2 = normal
- HCO3- = high
What is hypospadias?
Where the urethra opens on underside of penis
What would the pH, PCO2 and HCO3- be in metabolic acidosis?
- pH - low
- PCO2 - normal
- HCO3 - low
What are some causes of respiratory alkalosis?
- Hysterical over breathing
- High altitude
- Fever
- Brainstem damage
What is the compensatory mechanism involved in metabolic acidosis?
Increased loss of CO2 from lungs which reduces less H+, allowing pH to rise
Renal response - stimulates formation of ammonia and excretion of excess hydrogen ions - this mechanism takes a bit longer
What are some causes of metabolic acidosis?
- Ingestion of acids
- Excess metabolic production of H+ e.g. lactate acidosis or DKA
- Loss of HCO3- e.g. severe diarrhoea
- Renal disease e.g. failure to excrete H+
What would the pH, PCO2 be in respiratory acidosis?
- pH = low
- PCO2 = high
To compensate kidneys start to retain HCO3- and excrete H+ to raise pH
What are the histological changes in BPH?
Stromal-glandular hyperplasia within the prostate
- Circulating testosterone will directly affect both epithelial and stromal cells
- DHT mainly formed in stream cells which can move out in paracellular way
- Interacts with androgen receptors in epithelial and stromal cells
What are the compensation mechanisms for metabolic alkalosis?
- Respiratory compensation
- Increase in pH acts on chemoreceptors which reduce ventilatory rate and increase pCO2
What is a horseshoe kidney?
Where kidneys are malrotated and closer than they should be
What is epispadias?
Where the urethra opens on the dorsum of the penis
How does an absent kidney occur?
Absent kidney occurs if the collecting system (from ureteric bud) fails to fuse with the nephrons (from metanephric mesoderm)
What is urethral stricture?
Narrowing of the lumen which may be secondary to infection, trauma, extrinsic compression etc.
What are the risk factors for bladder/ureter/renal pelvis cancer?
- Smoking
- Arylamines
- Chronic irritation
What are risk factors for urolithiasis?
- Male
- Dehydration
- Dietary components
- Genetic factors
What is the difference between glomerulonephritis and glomerulopathy?
Glomerulonephritis - inflammation is present
Glomerulopathy - inflammation is absent
How does nephrotic syndrome lead to hyperlipidaemia?
Protein in the blood are leaked out and excreted in urine.
Overzealous body (liver) synthesises more lipoproteins, and reduced clearance of lipoprotein bearing lipoproteins.
Why does peripheral oedema occur in nephrotic syndrome?
- Overfill hypothesis: Increase salt and water retention
- Underfill hypothesis: reduced oncotic pressure in capillaries around the body due to protein loss, therefore fluid leaks out
What is focal segmental glomerulosclerosis?
Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome in children and adolescents, as well as a leading cause of kidney failure in adults.
Name 3 diseases nephrotic syndrome causes.
Focal segmental glomerulosclerosis
Membranous nephropathy
Minimal change disease
What is observed in minimal change histology?
normal on light microscopy but on electron microscopy - fusion of foot processes of podocytes
What is the epidemiology of minimal change nephropathy?
- Most common in children (but occurs in adults too)
- More common in males
- Main cause of nephrotic syndrome in children
How does minimal change nephropathy present?
Facial swelling (normally the first sign)
Ascites
Scrotal swelling
Peripheral oedema
What does damage of podocytes trigger?
Apoptosis causes popcytes to detach from glomerular basement membrane + be destroyed.
Glomerular basement membrane is exposed.
Maladaptive interactions develop between the glomerular basement membrane and the parietal epithelial cells.
This is followed by the proliferation of epithelial, endothelial, and mesangial cells.
The combination of cell proliferation and leak of protein into Bowman’s space results in the deposition of collagen.
Ultimately, the capillary loop collapses and endothelial cells are lost.
The glomerular tuft undergoes sclerosis, creating the characteristic lesion of FSGS.
The disease eventually progresses to produce global sclerosis and end-stage renal failure.
Why does proteinuria + hypoalbuminaemia occur once podocyte die?
Protein leaks across the glomerular membrane, resulting in proteinuria and hypoalbuminaemia.
At the same time, cholesterol levels rise due to increased cholesterol synthesis in the liver and the loss of lipid-regulating proteins in urine;.
Pathophysiology of minimal change nephropathy.
Unidentified circulating/permeability factors podocyte damage –> podocyte apoptosis
Less podocytes –> protein leaks
Proliferation of epithelial, endothelial, and mesangial cells –> proliferation and leak of protein into Bowman’s space deposition of collagen
Damage to capillary endothelial cells –> scarring
How are podocytes affected in primary FSGS?
More podocyte effacement, scarring and sclerosis more likely to be primary.
- Podocyte effacement is seen in normal and sclerosed glomeruli in primary
- Deeper glomeruli affected first
What are the problems with primary FSGS?
- Non responsive to steroid therapy
- Commonly recurs in transplanted kidneys
- Poor renal prognosis
- Later progresses to global sclerosis CKD (50% ESRD within 10 years)
What is secondary FSGS due to?
Underlying acquired disease
- Reduction in nephron no. e.g. hypertension, ischaemia, nephrectomy, IgA nephropathy
- Viruses e.g. HIV, cytomegalovirus, EBV
- Drugs e.g.heroin, anabolic steroids, lithium
What does reduced nephron number cause?
Greater blood flow in remaining nephrons which leads to glomerular hypertrophy and hyperfiltration.
What diseases does nephrotic syndrome in children cause?
Minimal change nephropathy
Focal segmental glomerulosclerosis
What diseases does nephrotic syndrome in adults cause?
Membranous glomerulopathy
Focal segmental glomeruloscleoris
Diabetic nephropathy
SLE
Amyloidosis
Amyloidosis?
It’s a rare disease that occurs when a substance called amyloid builds up in your organs.
Amyloid is an abnormal protein that is produced in bone marrow and can be deposited in any tissue or organ.
How does membranous glomerulopathy present?
Asymptomatic proteinuria or nephrotic syndrome (+/- haematuria, HTN, renal impairment)
What is membranous glomerulopathy secondary to?
Underlying pathology or toxic insult
What is sarcoidosis?
Sarcoidosis is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomas.
The disease usually begins in the lungs, skin, or lymph nodes.
Less commonly affected are the eyes, liver, heart, and brain. Any organ, however, can be affected.
What is SLE?
Systemic lupus erythematosus (SLE), also known simply as lupus, is an autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue in many parts of the body.
Symptoms vary between people and may be mild to severe.
HTN + renal impairment –> ?
Poor prognosis signs
What is diabetic nephropathy?
Microvascular complication of diabetes and elevated sugars
What are risk factors for diabetic nephropathy?
- Poor sugar control
- HTN (more insult to kidneys)
- Male
- Ethnicity (Southeast Asian)
- Social deprivation
What is diabetes mellitus characterised by?
High glucose levels and increased glomerular pressure, both of which can cause glomerular mesangium expansion via increased mesangial stretch.
What is nephritic syndrome.
Immunological disorder causing thickening of basement membrane
What are the signs of nephtitic syndrome?
- Hypertension (due to low GFR and increased Renin) (elevated JVP)
- Oliguria
- Oedema may be present (periorbital, sacral, leg)
- Acute kidney injury
- Azotemia
Causes of nephritic syndrome in children?
Haemolytic uraemic syndrome
Post-streptococcal GN
Henoch-schonlein purpura (IgA vasculitis)
What is haemolytic uraemic syndrome?
Damage to endothelium of glomerular capillary bed.
Nephritic syndrome
Hemolytic-uremic syndrome (HUS) is a disease characterized by a triad of hemolytic anemia (anemia caused by destruction of red blood cells), acute kidney failure (uremia), and a low platelet count (thrombocytopenia).
How does haemolytic uraemic syndrome present?
Haemolytic anaemia
Acute kidney failure (uraemia)
Thrombocytopenia (Thrombocyte – platelets, penia –> deficiency (in blood in this case)
List 2 causes for haemolytic uraemic syndrome.
Infectious agents e.g. streptococcus –> No diarrhoea
Toxigenic agent E.coli 0157.H7 –> Diarrhoea is present.
What is henoch schonlein purpura?
NEPHRITIC
Most common vasculitis of children (affects adults too)
Skin lesions are characterised as palpable purpura and are typically non-blanching.
The lesions are usually 2 to 10 mm in diameter, and represent the extravasation of blood into the skin.
Usually occur in crops and fade over several days.
Can occur anywhere, but are usually concentrated on the lower extremities.
The rash occurs in all patients.
What are the classic signs of henoch schonlein purpura (HSP)
- Rash (purpura) –> occurs in all patients
- Abdominal pain
- Arthritis/arthralgia
- Glomerulonephritis –> haematuria
- HSP can follow a URTI
What is post streptococcal glomerulonephritis?
Acute glomerulonephritis following streptococcal infection is characterized by the sudden appearance of hematuria, proteinuria, red blood cell casts in the urine, oedema, and hypertension with or without oliguria.
Occurs 1-3 weeks after streptococcal infection, e.g.
- Strep throat
- Otitis media
- Cellulitis
Why is there haematuria of post streptococcal glomerulonephritis?
Caused by a group A beta-haemolytic Streptococcus infection (usually Streptococcus pyogenes).
Leads to inflammation of glomerulus
But no necrosis
Causes of nephritic syndrome in adults?
- Goodpasture’s syndrome (anti-glomerular basement membrane disease)
- ANCA-associated vasculitis
- Mesangiocapillary glomerulonephritis
- IgA nephropathy (Berger disease)
- Systemic lupus erythematosus
What is goodpasture syndrome (GPS)?
NEPHRITIC
A rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure.
It is thought to attack the alpha-3 subunit of type IV collagen, which has therefore been referred to as Goodpasture’s antigen.
What does ANCA stand for?
Anti-neutrophil cytoplasmic antibodies (ANCAs)
- They are a group of autoantibodies mainly of the IgG type, against antigens in the cytoplasm of neutrophil granulocytes (the most common type of white blood cell) and monocytes.
Why is Goodpasture syndrome also known as anti-GBM glomerulonephritis.
Anti-GBM (anti-glomerular basement membrane antibodies attacks basement membrane)
2/3 good pastures (lung haemorrhage, due Ab attack on lung vasculature)
1/3 purely renal
Patients: >50, affect men + women equally
What does acute kidney injury lead to?
Acute decline in the GFR from baseline, with or without oliguria/anuria.
Which markers are used to diagnose acute kidney injury?
Creatinine in blood
Urine output
- Keypoint - AKI is potentially reversible
What are the pre-renal causes of acute kidney injury?
- Reduced renal perfusion: Hypovolemia, shock, low cardiac output (heart failure), haemorrhage
- Renal artery stenosis
What are the renal causes of acute kidney injury?
Tubular:
- Acute tubular necrosis
- Nephrotoxic drugs - NSAIDS, ACEi, gentamicin
Glomerular:
- Rapidly progressive glomerulonephritis
- Autoimmune
- Drugs
- Interstitial nephritis
Vascular:
- Vasculitis
- Thrombus
- Malignant BP (very high BP)
What are the post renal causes of acute kidney injury?
- Mechanical obstruction of the urinary outflow tract. e.g. lymphoma, tumour, prostate hyperplasia, strictures, renal calculi
- Ascending urinary infection (including pyelonephritis), and urinary retention
What are some important complications for AKI?
Hyperkalaemia - do U+Es + ECG
Uraemia - risk of encephalopathy and pericarditis
Why does intra-glomerular pressure increase in response to injury?
The kidney attepmpts to adapt to nephron loss to maintain constant glomerular filtration.
In CKD what can an increase in glomerular permeability to macro-molcules lead to?
An increase in glomerular permeability to macromolecules may result in toxicity to the mesangial matrix, causing mesangial cell expansion, inflammation, fibrosis glomerular scarring.
Give examples of macromolecules that the glomerulus may become more permeable to in CKD?
Transforming growth factor-beta (TGF-beta)
Fatty acids
Pro-inflammatory markers of oxidant stress
Protein
How is angiotensin II affected in renal injury?
Increases production, causing an upregulation of TGF-beta, contributing to collagen synthesis + renal scarring within the glomerulus
List 3 clinical indicators of CKD?
Microalbuminuria: 30 to 300 mg/g creatinine/day
Proteinuria: >300 mg proteinuria/day
Haematuria: >3 RBCs per high power field on more than 2 occasions
Risk factors for CKD.
- Age >50 years
- Male sex
- Black or Hispanic ethnicity
- Family history
- Smoking
- Obesity
- Long-term analgesic use
- Diabetes mellitus
- HTN
- Autoimmune disorders, genetic disorders e.g. polycystic kidneys
What is uremic pericarditis?
It causes fibrinous pericarditis + that is an exudative inflammation.
The pericardium is infiltrated by the fibrinous exudate.
This consists of fibrin strands and leukocytes.
Why is metabolic acidosis commonly associated w/ CKD?
As the number of functioning nephrons declines in CKD, acid excretion is initially maintained by an increase in the ammonium excreted per nephron.
Total ammonium excretion begins to fall when the GFR is below 40 to 50 mL.min.
How is CKD managed?
Main aim = slow progression by managing symptoms + dealing w/ cause.
Options:
- Dialysis
- Kidney transplant
List 5 anomalies of ureters.
Retrocaval /retroiliac ureter
Anomalies of ureteral diameter
Abnormal number of ureters
Partial doubling
Complete doubling
Explain partial doubling
Incomplete division of 2 ureters that fuse at different levels.
In each case a common section exists with a normal ureteral orifice.
A Uretero-ureteral reflux tends to occur at the Y branch.
Explain complete doubling
Here a complete doubling of the ureters, and renal pelvis occurs.
The ureters empty into the bladder in accordance with Weigart and Meyer’s law.
The calyx system of the upper renal pelvis is as not as well differentiated as that of the lower one.
This is often asymptomatic, unless there are complications due to the calyx system abnormalities.
Explain how there can be an abnormal number of ureters.
These are the most frequent anomalies of the urinary tract, and many are asymptomatic.
They arise from a premature branching of the ureter anlage, leading to a partial second ureter, or from an additional ureter anlage, when two complete ureters are generated.
Explain how there can be anomalies of ureteral diameter.
Primary megaloureter due to an obstruction:
- The cause of constriction of the terminal part of the ureter, leading to dilatation.
- The constriction can be anatomic, or purely functional.
- Above the constriction the ureter is dilated, bulging and the wall thickened.
- The primary megaloureter should be distinguished from the secondary due to a valve or a vesico-ureteral reflux.
Explain what retrocaval and retroiliac ureters are.
R ureter traces out an “S” at the L4 level behind the vena cava.
A developmental disorder of the vena cava is responsible.
In a similar manner the ureter can run behind the common iliac artery at the L5 level.
What is the most frequent type of anomalies of the urinary tract?
Abnormal no. of ureters.
What is congenital polycystic kidney (CPK)?
Polycystic kidney disease (PKD) is an incurable genetic disorder characterised by the formation of fluid-filled cysts on the kidney that multiply over time.
The kidney damage seen in PKD is thought to be the result of the body’s immune system, destroying the healthy tissue in its attempts to rid the kidney of the cysts.
What is infantile PKD caused by?
Autosomal recessive genetic mutation mapped to the short arm of chromosome 6 (6p21).
Both parents must be carriers of the mutation for their children to be affected with infantile PKD, with a probability of 25% that their child will be affected by infantile PKD.
Describe the phenotype of babies born with infantile PKD?
Floppy, low-set ears
A pointed nose
Small chin
Folds of skin surrounding the eyes (epicanthal folds).
Large, rigid masses can be felt on the back of both thighs (flanks), and the baby usually has trouble breathing.
What is renal agenesis?
Renal agenesis is a condition in which a baby is missing one or both kidneys at birth.
How may bilateral agenesis be manifest in utero?
BRA babies have distinct features, widely separated eyes, ears set too low, a flat broad nose, receding chin, and limb defects.
How does a horseshoe kidney form?
Horseshoe kidney is a renal fusion anomaly
Where is a horseshoe kidney found?
By the inferior mesenteric artery
The normal ascent of the kidney is impaired because the artery hooks over the isthmus
How is a horseshoe kidney connected?
90% by an isthmus of functioning renal parenchyma or fibrous tissue between the lower poles.
10% superior or both superior + inferior poles are fused.
What is a sigmoid kidney?
When either superior or both the superior and inferior poles of the kidney are fused
What is patent urachus?
Failure f the entire course of the urachus to close resulting in an open channel between the bladder and umbilicus.
It’s normally diagnosed when neonates leak urine from umbilicus.
What is exstrophy?
Means ‘turned inside out’
Bladder exstrophy is a congenital abnormality of the bladder
When does bladder exstrophy occur?
It occurs if lower abdominal wall does not form properly, resulting in a bladder which is open anteriorly and exposed on the anterior abdominal wall.
Pain from upper ureteral stones radiate where?
To flank + lumbar areas.
Stones obstructing the ureteropelvic junction present with what type of pain?
mild-to-severe deep flank pain without radiation to the groin.
On the right side (flank + lumbar areas), what can pain from upper ureteral stones be confused with?
Cholecystitis or cholelithiasis
What is cholecystitis?
Inflammation of the gallbladder.
What is cholelithiasis?
Gallstones
Which are concretions that form in the biliary tract, usually in the gallbladder
On the left side (flank + lumbar areas), what can pain from upper ureteral stones be confused with?
Acute pancreatitis
Peptic ulcer disease
Gastritis
What is gastritis?
Inflammation of the lining of the stomach.
It may occur as a short episode or may be of a long duration.
There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain.
Other possible symptoms include nausea and vomiting, bloating, loss of appetite and heartburn.
Where does miduretheral calculi pain radiate? What can this pain mimic?
Midureteral calculi cause pain that radiates anteriorly and caudally.
This pain can mimic appendicitis on the right or acute diverticulitis on the left.
Distal uretral stones cause pain that radiates where?
Into the groin / testicle (male) or labia majora (female) because the pain is referred from the ilioinguinal or genitofemoral nerves.
Which stones are rare?
Urate stones - they are radiolucent whereas most renal stones are radio-opaque.
What are renal stones commonly composed of?
Calcium oxalate
80% of the time
Which enzyme does allopurinol inhibit?
Xanthine oxidase
How does inhibition of xanthine oxidase reduce the amount of uric acid in the urine?
Inhibits the formation of uric acid from xanthine + hypoxanthine
How does leakage of calcium into urine lead to a change in the pH?
Alkalinisation of the urine
What is the physiological role of parathyroid hormone?
Primary response to PTH by kidney = to increase renal calcium resorption + phosphate excretion.
In the kidney PTH blocks reabsorption of phosphate in the proximal tubule + promote calcium reabsorption in the ascending loop of Henle, distal tubule, collecting duct.
What secreted PTH?
Parathyroid glands
Where in the nephron does parathyroid hormone block reabsorption of phosphate?
Proximal tubule
Where in the nephron does parathyroid hormone promote reabsorption of calcium?
Ascending loop of Henle
Distal tubule
Collecting duct
Why might primary hyperparathyroidism lead to the formation of calcium stones?
Primary hyperparathyroidism is the result of excessive secretion of PTH.
PTH regulates serum calcium + phosphate levels.
High levels of PTH causes serum calcium levels to increase and serum phosphate levels to fall.
This leads to excessive renal calcium excretion (hypercalciuria)
What is hypercaliuria?
Excessive renal calcium excretion
Urinary tract stones often lead to what?
Urinary stasis this can lead to infection
How does increased fluid intake reduce the chances of developing renal stones?
More fluid intake = more dilute urine = reduced concentration of ions within urine = reduces solubility product
What measurement on a dipstick urinalysis would be abnormal in a patient with urinary tract stones?
Blood is often present
pH will be normal in calcium oxalate stones but may be high in patients with type 1 renal tubular acidosis or in the presence of urease splitting microorganisms
Which measurements would be useful on serum biochemistry to determine the cause of the renal stone a patient had?
Calcium ion levels
Also check:
- pH
- 24 hour urine volume
- Oxalate
- Sodium
- Citrate
- Urate excretion
- Spot sample of cysteine
Where is angiotensinogen produced?
Liver
What does hydrolysis of angiotensinogen by renin give rise to?
Angiotensin I
What can ACE cleave aside from Ang I?
Bradykinin –> switching it off
What is the function of bradykinin?
Dilation of blood vessels
What does removal of bradykinin cause?
Less vasodilation
Increases the capability of Angiotensin II to increase blood pressure
Other than stimulating the secretion of aldosterone, what other effects are caused by angiotensin II?
- Constriction of blood vessels –> increased blood pressure
- Effects on nerves, causing thirst sensation, desire for salt
- Encouraging release of antidiuretic hormone from pituitary gland
- Effects on kidneys - increase sodium retention + water reabsorption
Therefore increases blood volume and pressure
Where is aldosterone secreted?
The zona glomerulosa of the cortex of the adrenal gland
As sodium is reabsorbed from the urine, what happens to blood volume and osmolarity?
Osmolarity of blood will increase as the sodium is reabsorbed.
The osmolarity increases as the ratio of solute to water molecules increases.
What effect does sodium reabsorption have on the blood pressure?
Blood volume will increase therefore blood pressure will increase.
Describe the MoA of angiotensin converting enzyme inhibitors (e.g. lisinopril, ramipril)
Block conversion of Ang I to Ang II thereby reducing arteriolar constriction and reducing blood pressure.
Also causes loss of sodium and water, leading to reduced blood volume.
And causes slight increase in potassium blood levels.
Describe the MoA of spironolactone.
Potassium sparing diuretic
Acts by antagonism of aldosterone in the distal renal tubules.
It competitively binds to the mineralocorticoid receptors; these are nuclear receptors that act via gene transcription that results in a decreased production and expression of both the ENaC and ROMK channels in the apical membrane, as well as decreasing the production and expression of Na+K+ATPase on the basolateral membrane.
These actions increase sodium + water excretion, while potassium is retained. Thus Spironolactone is a potassium sparing diuretic.
What clinical consequences may arise from horseshoe kidney?
Horseshoe kidneys generally function adequately but there is an increased incidence of upper urinary tract obstruction and infection.
Furthermore, it has also been reported that horseshoe kidneys can be associated with ureteric abnormalities including duplications (duplex ureters).
What are the S+S of polycystic kidney disease?
1) Pain or tenderness in the abdomen
2) Haematuria
3) Urinary tract infections (UTI)
4) Kidney stones
5) Symptoms of chronic renal failure
6) Asymptomatic hypertension
7) Asymptomatic presentation through family screening
What percentage does autosomal dominant polycystic kidney disease account for of all PKD cases?
90%
Autosomal dominant polycystic kidney disease 1 present at what age?
30-40s
Autosomal dominant polycystic kidney disease 2 present at what age?
60-70s
If symptoms of Autosomal dominant polycystic kidney disease presents in childhood then what might it be instead?
Autosomal recessive polycystic kidney disease
What is the goal of PKD treatment?
Control blood pressure
Reduce risk of cardiovascular complications
Reduce progressive kidney failure
What might PKD treatments include?
1) Pain medication
2) Blood pressure medication
3) Antibiotics (to treat UTI)
4) Low-sodium (salt) diet
5) Surgery (to drain cysts and help relieve discomfort – this is rare)
6) Novel therapies to alter cyst growth are in development
What is the meaning of infarct?
An area of tissue that undergoes necrosis as a result of obstruction of local blood supply, as by a thrombus or embolus
What are the causes of infarction?
The most common cause is thromboembolism from either the heart or aorta, or in situ thrombus formation within the renal artery or segmental branch artery.
Atrial fibrillation is a risk factor.
Why are renal infarcts typically wedge-shaped, as here?
This is due to the segmented nature of the blood supply to the kidney.
What would be the implications of this renal infarct for renal function?
It depends on the size of the infarct.
- Small infarcts do not affect kidney function, but multiple or large infarcts can lead to kidney failure, depending on the blood vessel that is occluded.
What symptoms and signs might you expect in small renal infarcts?
Often asymptomatic
What symptoms and signs might you expect in large renal infarcts?
Acute flank pain (mimicking renal colic) and maybe associated with haematuria.
What is hydronephrosis?
The swelling of a kidney due to a build-up of urine.
It happens when urine cannot drain out from the kidney to the bladder from a blockage or obstruction.
Hydronephrosis can occur in one or both kidneys.
What is the pelvicalyceal system?
Pertaining to the renal pelves and calices.
What is the renal parenchyma?
Parenchyma = the essential or functional elements of an organ, as distinguished from its framework, which is called the stroma.
Renal parenchyma = the functional tissue of the kidney, consisting of the nephrons.
What is the renal papillae?
The renal papilla is the location where the renal pyramids in the medulla empty urine into the minor calyx in the kidney.
Histologically it is marked by medullary collecting ducts converging to form a papillary duct to channel the fluid. Transitional epithelium begins to be seen.
What is hyperplasia?
The enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells, often as an initial stage in the development of cancer.
What causes bladder trabeculation?
Secondary to bladder outlet obstruction
Cause morphological + histological changes due to hypertrophy and hyperplasia of bladder muscle the infiltration of the connective tissue.
What treatments are available for prostatic hyperplasia?
Mild and moderate:
- Reduced alcohol consumption
- Exercise regime
Severe:
- Finasteride and dutasteride. 5-alpha reductase inhibitors. MoA: reduce dihydrotestosterone production and hence the activity of this hormone on the prostate gland, reducing its size and so improve symptoms.
- Tamsulosin, alfuzosin (alpha blockers), relaxant to aid urination.
- Surgery if prostate enlargement does not respond to treatment.
List common causes of hydronephrosis?
A blockage within the urinary tract between the renal pelvis and vesico-ureteric junction
A disruption in the working of the bladder leading to backflow of urine from the bladder to the kidney
1) Kidney stones
2) Pregnancy
3) Bladder or cervical cancer
4) BP hyperplasia or prostate cancer
5) Endometriosis
6) Tuberculosis
7) Pelvico-ureteric junction obstruction
8) Neurogenic bladder
9) Urethral obstruction
What are the consequences of outflow obstruction for the bladder?
Obstruction in the urethra causes bladder dilation, secondary hypertrophy and diverticulae formation.
What are the symptoms of renal cell carcinoma?
Typical symptoms of are:
1) Haematuria
2) Abdominal mass
3) Abdominal pain
4) Anorexia
5) Weight loss
6) Anaemia
7) Pyrexia
What is the most common type of kidney cancer in adults?
more likely to affect men in 50-70s
Renal cell carcinoma
What are risk factors for renal cell carcinoma?
1) Family history of the disease
2) High blood pressure
3) Horseshoe kidney
4) Polycystic kidney disease
5) Smoking
6) Von Hippel-Lindau disease (a hereditary disease that affects blood vessels in the brain, eyes, and other body parts)
What is the prognosis for patients with renal cell carcinoma?
Dependent on the level of metastasis, with the highest survival for those patients with early detection.
If however, the cancer has metastasised to the lymph nodes or to other organs, the survival rate is much lower.
Which factors predispose to transitional cell carcinoma?
The main factors driving the formation of this disease are environmental.
Therefore these are the main factors:
1) Smoking
2) Exposure to certain dyes/chemicals in leather/textiles/plastics and rubbers
3) The misuse of pain medicines
4) Exposure to some medicine – especially cyclophosphamide
How do the presenting features of transitional cell carcinoma depend on where it occurs in the urinary tract?
Haematuria is the most common presenting complaint, and this can be either visible or non-visible.
However if the tumour is present in the vesicouretic junction, this can cause obstruction of the ureter and hydronephrosis.
Alternatively if the tumour is present in the urethral orifice, then the patient may suffer from bladder outlet obstruction and urinary retention.
Unfortunately, occasionally patients sometimes only present after metastatic spread, due to systemic symptoms associated with the metastasis.
What are the complications of transitional cell carcinoma?
- UTI
- Urinary retention
- Hydronephrosis
- Recurrence of tumour
- • The risk of upper urinary tract tumour recurrence increases in patients with multiple and high-risk bladder tumours.
- Increased risk of urethral transitional cell carcinoma.
- Complications of surgery include bowel obstruction, obstruction of the ureter, pyelonephritis and infection of the wound.
- Radical cystectomy damages the S2,3,4 outlet and causes complete erectile dysfunction, although a nerve-sparing approach can reduce this to about half.
- Orthotopic bladders have a risk of urinary incontinence
What can radical cystectomy damage?
The S2,3,4 outlet and causes complete erectile dysfunction, although a nerve-sparing approach can reduce this to about half.
Which structure is commonly blocked by prostatic hyperplasia?
The prostatic urethra is commonly obstructed by benign hyperplasia
Which structure produces 60% of the seminal fluid?
Prostate
Where are openings of the ureters found?
Upper 2 corners of the trigone
Which structure is referred to as the trigone?
The trigone is at the base of the bladder, it’s made up by different cell types
What is the urachus?
A fibrous remnant of the allantois
What is the allantois?
A canal that drains the urinary bladder of the foetal that joins + runs within the umbilical cord
What biochemical change can cause cardiac arrest due to ventricular arrhythmia?
Raised serum potassium levels
What does raised blood renin lead to?
Hypertension
Erythropoietin deficiency is common in chronic kidney disease and leads to what?
Decreased red cell production
Normochromic, normocytic anaemia
What is the main vasomotor site of action of Angiotensin II?
Efferent arteriole
Where is the site of sodium reabsorption through a channel that is blocked by the diuretic furosemide?
Thick ascending loop of Henle
Where is the major site of bicarbonate reabsorption?
Proximal convoluted tubule
How does angiotensin II minimised constriction at the afferent arteriole?
Angiotensin II stimulates the release of the vasodilator nitric oxide from the afferent arteriole, thereby minimizing constriction at this site
How does furosemide work?
Furosemide is a loop diuretic.
It inhibits water reabsorption in the nephron by blocking the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle.
This is achieved through competitive inhibition at the chloride binding site on the cotransporter, thus preventing the transport of sodium from the lumen of the loop of Henle into the basolateral interstitium.
Where is bicarbonate reabsorbed in the nephron?
About 85 to 90% of the filtered bicarbonate is reabsorbed in the proximal tubule
The rest is reabsorbed by the intercalated cells of the distal tubule and collecting ducts.
Intravenous administration of which highly ionised drug, is very rapid plasma clearance by the kidney?
This drug has a low therapeutic index
Gentamicin
Aminoglycoside antibiotic
What is gentamicin?
An antibiotic that can be given via injection or intravenous.
It is part of the aminoglycoside family of antibiotics, which work via either preventing the growth of bacteria, or inducing bacterial death.
However, it may also cause some serious side effects, including damage to your kidneys and the cochlea in the inner ear, which controls hearing and balance.
The clearance of Gentamicin depends on both kidney function and body weight.
Indication of gentamicin
It is typically used for serious gram negative bacterial infections which are difficult to treat with other antibiotics.
To what structures can gentamicin cause damage to?
Kidneys
Choclea of inner ear
What is methly penicillin more commonl known as?
Penicillin V
Is penicillin V or G more effective against gram-negative bacteria?
G
Which antibiotic is more acid stable Penicillin V or G?
What are the implications of this?
V
Therefore can be given orally
What is lithium used to treat?
Bipolar affective disorder
Which univalent cation of the white metal series has a low therapeutic index and will accumulate rapidly in acute kidney injury?
Lithium
Where is lithium absorbed?
Lithium is absorbed by the GI tract, is not protein bound and is filtered at the glomerulus.
Where in the nephron is filtered lithium reabsorbed?
60% in the proximal tubule.
40% in the thick ascending limb of the loop of Henle, the connecting tubule, and the cortical collecting duct.
What can lithium be a substitute for in the nephron?
For sodium in several sodium channels
Particularly the sodium-hydrogen exchanger in the proximal tubule (NHE3), the sodium/potassium/2chloride exchanger in the thick ascending limb of the loop of Henle (NKCC2), and the epithelial channel of the cortical collecting tubule (ENaC).
Why will lithium levels rise rapidly and toxicity occur if patient on lithium develops acute kidney injury?
Because lithium is entirely renally excreted
Where does the left and right gonadal vein drain into?
L - left renal vein
R - directly into inferior vena cava
How do the gonadal veins ascend in the abdomen?
Along the psoas muscle
Anterior to ureters
Where does the renal artery arise from?
Abdominal aorta at L1-2, inferior to superior mesenteric artery
Pseudomonas spp. are gram-negative rod bacteria commonly found in where?
Soil, ground water, plants and animals.
Pseudomonal infection causes a necrotising inflammation.
What family are proteus species part of?
Enterobacteriaceae family of gram-negative bacilli.
Name bacterial species implicated as serious causes of infection in humans
Proteus, Escherichia, Klebsiella, Enterobacter, Serratia
Which bacteria species are commonly found in the human intestinal tract as part of normal human intestinalgl flora?
Proteus,
Escherichia coli,
Klebsiella,
Enterococci
Which physiological change will lead to an increase in the Glomerular filtration rate?
a. A decrease in renal blood flow
b. A decrease in the concentration of plasma protein
c. Compression of the renal capsule
d. Constriction of the afferent arteriole
e. Decrease in afferent arteriole pressure
A decrease in the concentration of plasma protein
Because GFR = (volume of urine x urine flow)/plasma protein concentration
When you reduce the denominator, the answer is greater (GFR)
What is the principal site for glucose reabsorption within the nephron?
Proximal convoluted tubule
What is the term that describes the volume of fluid from which a drug can be completely removed per unit of time (rate of drug removal)?
Clearance volume
When is clearance of a drug linear?
Clearance of a drug is linear if the drug is eliminated via first order kinetics.
Clearance of a drug can be completed via both renal excretion and liver metabolism, and in this case this clearances are additive (total clearance=clearance via the kidney + clearance via the liver).
A 45 year old woman presents with oedema of the face and ankles.
She is normally fit and well. Urine dipstick testing shows 4+ of protein, but no glucose or blood.
What is the likely pathological basis for this presentation?
An abnormality of the basement membrane of the glomerulus
What does proteinuria suggest?
Nephrotic syndrome
A 50 year old man has recently noticed ankle swelling.
Urine testing reveals non-visible haematuria and 4+ proteinuria.
What is likely to be causing the haematuria?
Glomerulonephritis
What is haematuria (often visible) without proteinuria suggestive of?
Bladder tumour
What does retroperitoneal fibrosis produce?
Renal obstruction at the level of the ureters and progressive renal failure.
What might you expect to find as a ‘normal variant’ on inspection of the urine of a dehydrated patient?
A. Glucose B. Granular casts C. Hyaline casts D. More than 10 white cells per cubic millimetre E. Red cells
Hyaline casts - found in healthy individuals who are dehydrated or who do vigorous exercise.
What are hyaline casts formed from?
Excess (Tam-Horsfall) protein in the nephrons
A 35 year old woman presents with her first episode of symptoms of urinary frequency and painful micturition. She is normally fit and well Her urine is cloudy and blood, protein and nitrites are detected on a dipstix test.
Which antibiotic is the most appropriate choice in this situation?
This is a simple (as opposed to complicated) urinary tract infection.
The most common organism is E. Coli which responds well in most circumstances to trimethoprim which is also a cheap drug.
What is nitrofurantoin used for?
List it’s pros and cons.
Treating bacterial urinary tract infectious that are not caused by Proteus ssp.
Nitrofurantoin is concentrated in the urine and is a reasonable choice but not active against Proteus ssp.
A 35 year old woman presents with her first episode of symptoms of urinary frequency and painful micturition. What is the most reliable guide to the presence of a bacterial infection in the urine?
Nitrites in urine
How are nitrites formed
nitrate (NO3) –> nitrite (NO2)
catalysed by bacterial nitrate reductase
When might presence of. nitrites be falsely negative in a urine dipstick (when there is a bacterial infection)?
if infections caused by non-nitrate reducing bacteria
low no. of bacteria
patient taking vitamin C
A 76 year old man presents with severe kidney failure. Examination confirms a suprapubic mass consistent with an enlarged bladder.
What pathology is most likely to result in this presentation?
Benign hyperplasia of the prostate gland
An 82 year old woman presents with a history of nocturia and polyuria. Blood tests show severe kidney failure. You suspect a diagnosis of post-renal kidney failure.
What imaging technique would you request to demonstrate this pathology? And why?
Ultrasound
- cheap
- non-invasive
- doesn’t involve ionising radiation
- doesn’t involve administration of. potentially nephrotoxic iodinated contrast
Bladder cancer is most likely to cause obstruction at which level?
Vesico-ureteric junction
In which case the bladder would be empty
What would an ultrasound reveal in post-renal kidney failure?
Hydronephrosis
Distention of the renal calyces and pelvis with urine as a result of obstruction of the outflow of urine distal to the renal pelvis.
How is the renal clearance of a drug affected by the urine pH level?
Acidic pH aids basic drugs to be excreted
Basic pH aids acidic drugs to be excreted
Which part of the nephron is the primary site of action of the thiazide diuretics?
Distal tubule (early)
Inhibit the sodium-chloride cotransporter in the distal tubule
Why are thiazide diuretics less powerful than loop diuretics?
Because they act on the distal tubule where only 5% of filtered sodium is reabsorbed (less than from the loop of Henle - 20-30%)
A pharmaceutical company wishes to undertake a study of a new drug that may alter kidney function.
In their initial studies they need to measure GFR as precisely as possible in normal volunteers.
Which test would give the most accurate measurement of glomerular filtration rate?
Inulin clearance
Inulin is the most accurate substance to measure because it is a small, inert polysaccharide molecule that readily passes through the glomeruli into the urine without being reabsorbed by the renal tubules.
What does the intermediate mesoderm develop into?
Urogenital system (kidneys + gonads) + their respective duct systems
Adrenal cortex
At 3rd week of foetal development the intermediate mesoderm differentiates into the kidneys.
What are apices of renal pyramids surrounded by?
Minor calyces which join to form a major calyx which unite to form the renal pelvis which exit the kidney to form the ureters
During development when do kidneys ascending to assume their adult position?
~9th week
Which structure typically prevents the normal ascent of a horseshoe kidney?
Inferior mesenteric artery
What does renal pyramids consist of?
Tubules that transport urine from the cortical part of the kidney to the calyces
What is the point of each renal pyramid called?
Papilla
What pathophysiological mechanism can lead to a sudden fall in GFR following the commencement of treatment with an ACE Inhibitor?
Efferent arteriolar vasodilatation
Due to inhibition of Ang II which is a vasoconstrictor.
How does inhibition of ACE affect bradykinin levels?
Increase them
- because ACE inactivates bradykinin when it’s not being inhibited
What is bradykinin?
A potent vasodilator
Where does acetazolamide (carbonic anhydrase) act in a nephron?
Proximal tubule
Where does amiloride and spironolactone act in the nephron?
Inhibition of aldosterone receptor at the distal tubule and cortical collecting duct,
Where does furosemide act?
Ascending limb of the loop of Henle
Na-K-2Cl transporters
Where does bendroflumethiazide work?
Bendroflumethiazide is a thiazide diuretic which works by inhibiting sodium reabsorption at the beginning of the distal convoluted tubule (DCT)
via Na-Cl transporter
What are the most powerful diuretics?
Loop diuretics which act on ascending loop of Henle
Examples of loop diuretics
Furosemide
Bumetanide
Dichlorphenamide
Methazolamide
Loop diuretics contraindications.
Anuria;
Comatose and pre-comatose states associated with liver cirrhosis;
Renal failure due to nephrotoxic or hepatotoxic drugs;
Severe hypokalaemia;
Severe hyponatraemia
Where do thiazides, chlorothiazides, hydrochlorothiazides (diuretics) act?
Distal convoluted tubule
Where do potassium sparing antikaliuretic diuretic agents work?
Collecting tubule and duct
Upper urinary tract infection pain is localised where?
Loid pain which may radiate to groin/testicles
What causes dark urine?
Concentrated bile pigments
What causes frothiness of urine?
Excess protein
What does urobilionogen in urine dipstick mean?
It is a breakdown product bilirubin which suggests haemolysis
Creatine is broken down in muscles, what is the by-product of this catabolism?
Creatinine - used to estimate GFR and hence kidney function
What are the following symptoms indicative of?
o Urinary frequency (e.g. cystitis) o Nocturia o Urgency o Incontinence o Bladder pain o Dysuria
Storage issues lower urinary tract
List obstructive voiding symptoms (lower urinary tract).
o Hesitancy o Delay in initiating micturition o Weak urinary stream o Straining to void o Incomplete emptying o Terminal dribbling
As per the endocrine functions of the kidneys, the kidneys produce which 3 important hormones?
- Erythropoietin
- Calcitriol (1,25- dihydroxycholecalciferol)
- Renin
They also synthesize prostaglandins (not unique to kidneys), which affect many processes in the kidneys .
Which kidney is slightly lower than the other?
Right kidney - due to liver
Name 5 renal regions.
Bowman’s capsule (cup-shape + surrounds glomerulus) Proximal convoluted tubule (PCT) Loop of Henle (LoH) Distal convoluted tubule (DCT) Collecting duct (CD)
The glomerular capsule has 2 layers.
Visceral and parietal, describe their histology.
Between the 2 layers lies the capsular space (lumen of urinary tube)
Visceral layer (inner): • Podocytes (modified simple epithelial cells) – stop macromolecules passing • Pedicles (foot-like projections) wrap around endothelial cells of glomerular capillaries to form inner capsule wall • Fenestrated endothelium
Parietal layer (outer): • Simple squamous epithelium
What lies between the parietal and visceral layers of the glomerular capsule?
Capsular space aka lumen of urinary tube
What is the function of the capsular space?
Fluid filtered from glomerular capillaries enters this space
Describe the histology of the PCT.
- Have apical microvilli - increased SA for absorption + secretion
- High no. of mitochondria
Histology of the descending limb of the loop of Henle and the thin ascending limb
Simple squamous epithelium
What do cortical nephrons lack?
Thin ascending limb of loop of Henle
Histology of thick ascending limb of loop of Henle
- Simple cuboidal to low columnar epithelium
- Final part of ascending limb makes contact w/ afferent arteriole (because columnar tubule cells in this region are crowded together they as known as macula densa)
What type of cells lie alongside macula densa?
Wall of afferent arteriole (and sometimes effect) containing modified smooth muscle fibres (juxtaglomerular cells)
Function of juxtaglomerular apparatus
Regulate blood pressure
and filtration rate of the glomerulus
Name the cells in the kidney that synthesize, store and secrete renin.
They are specialised smooth muscle cells mainly in the walls of the afferent arterioles and some in the efferent arterioles.
The juxtaglomerular cells (JG cells, or granular cells)
What begins a short distance past macula densa?
Distal convoluted tubule cells
In the last part of the DCT and collecting duct what cells are present?
Principal cells and intercalated cells
Function of intercalated cells?
Maintain acid-base balance
Function of principal cells?
Reabsorb Na+ and secrete K+
What 2 ways can K+ secretion be increased?
K+ secretion can be increased by aldosterone + by increasing Na+ delivery to CD
Which part of the kidneys have receptors that bind ADH (vasopressin) and aldosterone?
Collecting duct
Where do collecting ducts drain into?
Large papillary ducts
What are papillary duct cells lined with?
Simple columnar epithelium
Is glomerular filtration passive or active?
Passive process in which hydrostatic pressure forces fluids and solutes through a membrane
What do podoytes prevent?
Prevents macromolecules from travelling further
What does the basement membrane in kidneys prevent?
Plasma proteins from entering capsular space
What is tubular reabsorption and tubular secretion?
o Tubular reabsorption: movement of solutes + water from lumen of renal rubble across epithelial cells + back into blood
o Tubular secretion: movement of solutes directly from blood across the epithelial cells into luminal filtrate
What does aldosterone do?
Increases sodium reabsorption which increases water reabsorption which leds to more concentrated urine
Increases sympathetic activity
Stimulates posterior pituitary gland to secrete ADH, which causes water reabsorption in collecting duct which increases concentration of urine
What are the branches of the renal arteries called?
The segmental arteries are branches of the renal arteries.
There are 5 named segmental arteries:
- superior
- inferior
- anterior superior
- anterior inferior
- posterior
Name the arteries which which supply the renal lobes.
Interlobar arteries
Where does the renal veins lie relative to the renal arteries?
Anterior
Which renal vein is longer and why?
The left renal vein is longer because the vena cava lies slightly to the right so the vein travels anteriorly to abdominal aorta
Lymph from kidneys drain where?
Into lateral aortic nodes located at origin of renal arteries
NaCl is actively transported out of which limb of the loop of henle?
What does this do?
Ascending limb
This increases interstitial fluid osmolality + creating an osmotic gradient
Where is water passively transported out of?
The descending limb of LoH (down it’s conc. gradient)
Common causes of chronic kidney disease?
Diabetes
LT uncontrolled hypertension
Polycystic kidney disease
Why is creatinine used to measure GFR?
Freely filtered, not secreted, not absorbed
WHat filters out of the blood at the glomerulus and what does not unless there is pathology?
Blood cells + proteins don’t filter through unless there’s pathology
NaCl, K+, H2O, glucose, aa, creatinine, urea filter out
The proximal convoluted tubule lies in the renal cortex. What is absorb here?
Na+ (65%)
H2O (65%)
HCO3- (90%)
Cl- (50%)
Glucose + aa (~100%)
What is secreted in the PCT?
Uric acid + organic acids are secreted into nephron from capillaries
The primary role of the loop of henle is what?
Concentrate the salt in the interstitium
What is the descending limb of the loop of Henle permeable to? And what is it impermeable to?
Permeable to water + impermeable to solutes (salt particles)
What is the ascending limb of the LoH permeable and impermeable to?
Impermeable to water + actively transports NaCl to interstitial fluid of medullary pyramids
What is the renal corpuscle made up of?
- Glomerulus (capillary network)
* Glomerular capsule (Bowman’s capsule) – double walled epithelial cup surrounding glomerulus
What is the 3 main sectionsl of the renal tubule?
- Proximal convoluted tubule (PCT) – renal cortex
- Nephron loop (LoH) – renal medulla
- Distal convoluted tubule (DCT) – renal cortex
Differences between thin and thick ascending limb histology.
Thin ascending limb – lumen same as other areas but thinner simple squamous epithelium
Thick ascending limb – thicker simple cuboidal epithelium
Name the 2 classes of nephrons.
Cortical nephrons (majority)
Juxtamedullary nephrons
Describe the cortical neprhones
Renal corpuscles – lie in outer portion of real cortex
Short loops of Henle – lie mainly in cortex + penetrate only into outer region of renal medulla
Blood supply – peritubular capillaries (that arise from efferent arterioles)
Describe the juxtamedullary nephrons
Renal corpuscles – lie deep to cortex, close to medulla
Long loops of Henle – extend deep into medulla
which enable kidneys to excrete v. dilute or conc. urine
Blood supply – vasa recta (that arise from efferent arterioles)
Do cortical or juxtamedullary nephrons have longer loops of Henle?
Juxtamedullary
Summaries histology of the different parts of the renal tubule.
PCT = Simple cuboidal w/ prominent microvilli
LoH (descending + thin ascending) = Simple squamous
LoH (thick ascending )= Simple cuboidal + low columnar
DCT (majority) = Simple cuboidal
DCT (last part) + CD = Simple cuboidal w/ principal + intercalated cells
What is the major stimuli that triggers release of Ang II?
Low blood volume/pressure causes stimulation of renin-induced Ang II production
What major stimuli triggers aldosterone release?
Increased Ang II level + increased plasma K+ level –> promote aldosterone release by adrenal cortex
What stimulates ANP (atrial natriuretic peptide) secretion?
Stretching of atria
Causes of urological pathology.
Congenital, infection, inflammation, stones, cancer, trauma, neurological
Describe what horse-shoe kidney is?
- Kidneys rotated lying lower than normal, over poles close together, bridge of tissue between kidneys
- Kidneys have failure to depart from midline
What is BPH associated with histologically?
Histological changes of stromal-glandular hyperplasia seen within the prostate
When is benign prostatic hyperplasia clinically significant?
When this overgrowth of benign tissue is associated with bothersome lower urinary tract symptoms: frequency, urgency, nocturia, weak stream
The enzymes aromatase and 5-alpha reductase are responsible for converting androgen hormones (aromatase, 5-alpha reductase) into what?
Aromatase = oestrogen
5-alpha reductase = DHT
DHT is a potent anabolic hormone that promotes what?
Prostate cell proliferation
What is urolithiasis?
Formation of stony concretions in the bladder or urintary tract
What percentage of stones are made up of: calcium (oxalate + phosphate), uric acid, struvite (magnesium ammonium phosphate)?
Calcium stones: 75-80% (oxalate + phosphate)
Uric acid: 4-15%
Struvite (magnesium ammonium phosphate): 4-12% (F>M), urease producing bacteria – staghorn calculus
What is the commonest cancer in men?
Adenocarcinoma of prostate
90% of over 90 year olds
What is rate of drug elimination known as?
Clearance
What is volume of distribution?
Fluid volume that would be required to contain the amount of drug present in the body at the same conc. as in the plasma
List drugs than can cause acute interstitial nephritis?
Beta-lactam antibiotics, vancomycin, NSAIDs, furosemide, thiazides
What are aminoglycosides?
Bactericidal antibiotics which act by inhibiting bacterial protein synthesis
Why can’t you give aminoglycosides to patients with renal failure?
Decreased clearance, this can lead to excess levels of the drug building up + causing ototoxicity
Half-life of aminoglycosides:
• Healthy patients: 1.5 hours
• Renal failure patients: 25 hours
Which drugs can cause ototoxicity?
Aminoglycosides and loop diuretics
Which antibiotics cause tubular toxicity?
Aminoglycosides
Tetracyclines
Where do carbonic anhydrase inhibitors act?
Proximal tubule
Where does osmotic diuretics act?
In the nephron, osmotic diuretics act at the portions of the nephron that are water-permeable.
Proximal convoluted tubule and the descending limb of Henle’s loop.
Where do thiazides, chlorothiazides, hydrochlorothiazides act?
DCT
What are furosemide, bumetanide, dichlorphenamide, methazolamide examples of and where do they work?
Loop diuretics
Inhibit Na+/K+/2Cl- co-transporter in thick ascending limb
What causes nephrotic syndrome?
Loss of function of glomerular basement membrane
Common primary causes of nephrotic syndrome in children?
- Minimal change glomerulonephritis (MCG)
* Focal segmental glomerulosclerosis (FSGS)
Common primary causes of nephrotic syndrome in adults?
- Focal segmental glomerulosclerosis (FSGS)
* Membranous glomerulonephritis - Second most common nephrotic disease in adults after FSGS
List secondary causes of nephrotic syndrome?
Diabetic nephropathy
Systemic Lupus Erythematosus (SLE)
Amyloidosis
Chronic viral infection
Causes of acute renal injury
o Glomerular injury (irreversible)
o Interstitial injury
o Acute tubular necrosis
Names of nephritic syndrome in adults.
- Goodpasture’s syndrome
- ANCA-associated vasculitis
- SLE
- Mesangiocapillary NG
- IgA nephropathy (Berger disease)
Treatment of nephrotic syndrome.
Water given with negative balance
High protein and high calcium
Salt restriction and potassium given freely
Treatment of nephritic syndrome.
Water with negative balance (less than normal as pt. is hypervolemic)
Sodium, potassium, protein restriction
In nephritic syndrome which 2 immunological disorders cause thickening of the basement membrane?
Anti-basement membrane antibody (Goodpasture’s)
Immune complex (ppt of BM)
What is the mechanism of nephrotic syndrome?
Any inflammation causes proteinuria then oedema then hypovolemia then more hypoalbuminemia and hyperlipideia
How much urine does the bladder normally store?
300-400ml
Histology of the lower urinary tract
o Outer – adventitial connective tissue layer
o Middle – smooth muscle coat (detrusor)
o Innermost – transitional cell epithelium – an elastic barrier that is impervious to urine
How does the urethra differ in males and females?
Urethra is 5 times longer in males
Urethra is divided into 3 segments in males, but is 1 short tube in females
Urethra is a common duct for the urinary + reproductive system in males (separate in females)
What are the nerve roots for micturition?
S2-4 (parasympathetic)
Which nerve controls bladder contraction and which nerve controls relaxation of sphincter?
o Pelvic nerve (efferent + afferents) control bladder contraction
o Pudendal nerve S2, S3 – relaxation of sphincter
Commonest cause of UTI
UTI-causing (uropathogenic) E. coli (UPEC
Risk factors for UTI
- Female sex (shorter urethra)
- Anatomic abnormality
- Functional abnormality
- Neurological disorders (spinda bifida, MS)
- Catherisation
- Pregnancy
- Foreign body (e.g. stones)
- UT surgery/instrumentation
Name some viruses which can cause UTIs
Adenoviruses
Associated w/ haemorrhagic cystitis
BK + JC viruses
Associated w/ infection + graft failure in patients following kidney transplants
List host defences against UTI
Urine flow and micturition
Urine chemistry (osmolality; pH; organic acids)
Secreted factors
o sIgA (secretory IgA)
o Lactoferrin: an iron chelator
Mucosal defences
o Mucopolysaccharides – glucoseaminoglycan
o Few receptors
Name the 3 routes of acquisition of a urinary infection.
Ascending (commonest)
- Bacteria transmitted from bowel to urethra then to bladder then to kidney
Haematogenous
Lymphatic spread
List gram-negative bacteria than can cause UTIs
Klebsiella
Enterobacter
Serratia
Pseudomonas aeruginosa
Proteus mirabilis
List gram-positive bacteria than can cause UTIs
Staphylococcus epidermidis
S. aureus
S. saprophyticus
Enterococcus faecalis
50% of women w/ clinical features of cystitis have negative urine cultures. What are the possible explanations?
o Low bacteria count –> low nitrites
o Fastidious bacteria which don’t grow on routine culture media – e.g. ureoplasma
o Non-infective inflammation
o Sexually transmitted pathogens – e.g. chlamydia trachomatis
Which antimicrobial agent is not active against proteus species so should not be given if that is the cause of a UTI?
Nitrofurantoin
Which antimicrobials are given for lower urinary tract infections?
Amoxicillin (high resistance)
Trimethoprim
Cephalexin
Which antimicrobials should be given in a mild and severe upper UTI?
o Upper tract (mild): co-amoxiclav
o Upper tract (severe): cefotaxime, gentamicin
List the types of urinary incontinence.
Urge incontinence due to an overactive bladder
Stress incontinence due to poor closure of the bladder
Overflow incontinence due to either poor bladder contraction or blockage of the urethra
Functional incontinence due to medications or health problems making it difficult to reach the bathroom
How secondary hyperparathyroidism, due to poor kidney function, leads to bone and joint pain?
Patient’s decreasing kidney function has resulted in kidneys not being able to convert enough vitamin D to its active form and they are also not able to adequately excrete phosphate.
Due to this insoluble calcium phosphate forms, removing calcium from the circulation, which results in hypocalcemia.
The parathyroid glands detect this and secrete parathyroid hormone to try and raise serum calcium levels.
This is achieved through several mechanisms, including increasing the osteoclastic activity of bone, resulting in renal osteodystrophy.
Which part of the renal tubule is the 90% of sodium carbonate (Na2CO3) reabsorbed?
Proximal tubule
