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
