renal strand Flashcards
what are 3 functions of the kidneys
- remove toxins, excess water and waste products
- vital role in BP
- activate vitamin D
what things put individuals at risk of chronic kidney disease/CKD
- diabetes
- high BP
- heart and circulatory disease
- family history of CKD
- black/ asian minority
what is a nephron
a filtering unit
what is the outer area of the kidney called
the cortex
what is the middle region of the kidney called
the medulla
what is the blood supply to the kidney
renal vein and renal artery
where do we usually get collection of stones in the kidney
ureter - causing narrowing
list the journey the blood would take as it enters the kidney via the renal artery and leave via the renal vein
renal artery –> afferent arteriole –> bowman capsule –> glomerulus –> efferent arteriole —> peritubular capillaries —> vasa recta –> renal vien
where is the fluid leaked out of the blood supply and into the filtration system in the nephrons ? what blood vessles are involved here
fluid leaked out when the blood enters the glomerus into the bowmans space of the bowmen capsule
via the fenestrated capillaries and the basement membrane
highlight the steps the flitrate flows through in the kidneys
bowmans capsule –> bowmans space –> proximal tubule –> ascending loop of Henle –> descending loop of Henle –> distal tubule –> collecting duct
how are the nephrons arranged in the kidney
placed horizontally end to end
what are the 2 broad functions of the kidney
- homeostasis (maintenance of internal environment)
- hormone secretion (endocrine function)
how does the kidney maintain fluid and electrolyte balance ? what electrolytes does it control the levels of
maintains
- volume status : regulates the fluid balance through urine
- electrolyte levels: Na+, K+, Urea and creatinine
- osmolarity (conc of particles excepting an osmotic pressure)
how does the kidney regulate the acid base balance
maintains the optmimum pH for cellular function through bicarbonate regeneration in the proximal tubule
what small molecules does the kidney reabsorb
sugars and AA
what does the presence of sugars in the urine indicate
diabetes
tubular disorders
what does the presence of AA in the urine indicate
disease of the primal tubule
what does the kidney excrete
waste products
drugs
what are waste products produced by the kidney
nitrogenous waste products from protein metabolism:
urea and creatinine
what is creatine related from? why are its levels measured in the blood
muscle
used to measure kidney function
what kind of drugs can accumulate in the kidneys in kidney disease
- antibiotics (eg. penicilin)
- digoxin
- opiates
- lithium
how does the kidney stimulate RBC production / erythropoiesis ? what do patients with kidney disease develop
release erythropoietin which stimulates production off RBC
patients with kidney disease develop anaemia
what stimulates the production of RBC in the kidneys
hypoxia
why do athletes train at high altitudes
because hypoxia stimulates the release of
erythropoietin in the kidneys and so stimulates RBC production
what does the kidney release in order to maintain calcium phosphate balance
activated from of vitamin D
what is the activated form of vitamin D called
1,25 dihydroxy cholecalciferol
form calciterol
where does the first and second stage of hydroxylation of vit D happen
first stage happened on the liver
second stage happens in the kidneys
where do calcium and phosphate get absorbed and excreted
absorbed form the gut/small intestine and excreted by the kidneys
what does calciterol induce
increases the absorption of calcium and phosphorus in the gut and the release of calcium and phosphorus in the bone
what gland detects low calcium levels and how does it respond
parathyroid gland detects low calcium levels and responds by releaseing PTH/ parathyroid hormone
what can low levels of calciterol cause
bone disease
in chronic kidney disease there is a decreased
- activation of vit D
- level of calcium
levels of which hormone is increased in CKD? what can this lead to and why is this dangerous?
levels of parathyroid hormone increase
can lead to secondary hyperparathyroidism= increases release of calcium from bone = bone disease
what disease is associated with CKD and why
renal osteodystrophy - increased risk of fractures and anemia due to fibrosis of the bone
how does the kidney control BP
through renin secretion
do patents with CKD have high or low BP
often have high BP due to damage of kidney (angiotensin 2 released due to low blood flow through kidney)
what blood test investigations do we do in someone with CKD
- urea and electrolytes
- bicarbonate
- chloride
what do you test for in a urea and electrolyte test
- Na
- K
- urea
- creatine
what is the normal range for Na levels in a urea and electrolyte test
133-146 mol/L
what is the normal range for K levels in a urea and electrolyte test
3.5-5.3 mmol/L
what is the normal range for urea levels in a urea and electrolyte test
2.3-7.5 mmol/L
what is the normal range for creatine levels in a urea and electrolyte test - remember this varies in males and females
male: 64-104 mol/L
female: 60-93 mol/L
why are normal levels for creatine lower in females than males
because males have an increased muscle mass in comparison to females
what is the normal range for bicarbonate in a blood test
22-29 mmol/L
what is the normal range for chloride in a blood test
95-108 mmol/L
what does a failure in bicarbonate regeneration of the kidneys lead to
decreased bicarbonate can lead to the patient becoming acidemic which effects cellular function
what can increased levels of urea in CKD lead to
pericarditis (inflammation of heart)
seizures
confusion
what do we check for in a urinalysis (urine test, the test strip ones )? what does their presence suggest?
pH haematuria - not normal proteinuria - not normal Glucose - diabetes Nitrates - infection Leucocytes - infection
what is specific gravity a measure of
whether someone can conc their urine
what do we see in a urinalysis of someone with a UTI
- Blood trace
- nitrogen postive
- leukocyte positive
what do we see in a urinalysis of someone with a glomeritus (inflammation of the kidney)
- blood
- protein
what do we check for in an actual 2ml urine sample (ie. not the strip/urinalysis)
- protein/creatinine ratio
- albumin/creatine ratio
- midstream urine
what are normal levels for protein/creatine ratio
<13.0 mg/mmoL
what are normal levels for albumin/creatine ratio
<3.0 mg/mmoL
what is midstream urine
clean catch of urine - sent if suspected UTI
what do we check in an ultrasound of the kidney
- check the size of the kidney (small kidneys indicate CKD- scarred)
- any obstruction in the kidney
why would we perform a kidney biopsy
to diagnose some forms of kidney disease - guided by ultrasound
what are the complications of performing a kidney biopsy
risk of bleeding (1 in 100)
risk of losing a kidney (1 in 1000)
what would we observe in a histological biopsy of someone with focal segmental glomeruloscelerosis (a diseased kidney)
- diseased glomerluous recognised by deposition of fibrotic material in the glomerulus
what does the glomerular filtration rate measure
how much blood your kidneys filter per min
what is the normal glomerular filtration rate
100-120 mls/min
why is it hard to get an accurate measure of glomerular filtration rate
time consuming and requires the injection of a radioactive catheter
what is creatine clearance
an estimation of globular filtration rate
which is more accurate, creatine Clarence or glomerular filtration rate
glomerular filtration rate is more accurate than creatine clearance
how do you obtain the measure for creatine clearance
a blood test and 24 hour urine collection
what is creatine released by
muscle
what is creatine filtered and removed by
the kidneys - additional removal of creatinine is by secretion into the filtrate by the proximal tubule of the kidneys
what are the normal ranges for male and female serum creatine levels
64-104 mol/l - male
60-93 mol/L - female
when do serum creatine levels increase
kidney disease
in what case do we get a delay in rise of serum creatine levels
following acute kidney injury
is serum creatine specific or non specific
not specific for the site of injury
what is the estimated glomerular filtration rate measured by - eGFR
Automatically calculated by laboroties
what variables are used to calculate eGFR
- age of patient (kidney function declines with age)
- sex of patient (males have higher average muscle mass)
- serum creatinine
what is a correction factor which is used in the calculation of eGFR? in who and why do we use it
used for increased muscle mass based on race
a correction factor of x1.2 for black people is used based on average increased muscle mass
what does eGFR estimate
the % kidney function - which is useful when discussing with patients
does eGFR decrease with age
yes - goes to about 90 in 40-59 its and about 75 in older than 75
at what level of eGFR will patients need to carry out dialysis
<10 mls/min/1.73m2
at what level of creatine is 50% of kidney function lost
by the time the creatine level rises above 104 mol/L in male
what is the function of the convoluted tubule
recovers 70% of glomerular filtrate
what kind of things are recovered by the proximal convoluted tubule
- water - by aquaporins
- electrolytes
- glucose
- AA
- and recovery and re-generation of bicarbonate (to maintain acid-base balance)
what enzyme is the regernation of bicarbonate dependent on in the proximal convoluted tubule
carbonic anhydrase - combines CO2 and H20 to form H2CO3 and into HCO3-
what drug inhibits the action of carbonic anhydrase ? what is this drug used for
acetazolamide - used in altitude sickness : hypoxia, hyperventilation, respiratory alkalosis
what are the 2 types of kidney disease we can have
acute and chronic
how is the function of the proximal convoluted tubule effected by kidney disease
failure to regenerate bicarb can lead to academia (metabolic)
what happens in the ascending limb oh Henle
uptake of:
- Na+
- K+
- 2CL-
- H20
on what part of the nephron and how do the loop diuretics work?
work of the ascending limb of Henle
act to remove the fluid form the patient but inhibiting co-transporter uptake which results in the loss of electrolytes and water
what kind of patents receive loop diuretics
- heart failure
- CKD
- nephrotic syndrome
what happens in the cortical collecting duct
site of reabsorption of Na+ (with water and Cl) in exchange for K+
what hormone controls the reabsorption in the collecting duct
aldosterone
how is the action of the cortical collecting duct inhibited
by spironolactone - diuretic
what can problems in the cortical collecting duct lead to
heart failure
acscites
so use dirurectics (spironolactone) to treat
what part of the nephron is in the medulla of the kidney
loop of hence and medullary collecting duct
what happens in the medullary collecting duct
site of urinary conc
what hormone controls the action of the medullary collecting duct
ADH - increases water reabsorption through aquaporins
why would we get an increased secretion in the medullary collecting duct
due to fluid loss through:
- haemorrahage
- burns
- vommitng and diarrhoea
what is osmolality
number of particles of solute per kg of convent
what is molecules effect osmolality
Na
urea
glucose
how is osmolality calculated
(2 x Na+) + glucose + urea
what is plasma osmolaty normally maintained at
275-290 mOsm/Kg
what does rising osmolity trigger
thist
ADH secretion
what is the normal range for urine osmolality
500-850 mOsm/Kg
what is the normal daily output of urine
1.5-2 L
why do the kidneys concentrate urine at times of decreased fluid uptake
to conserve salt and water
to maintain circulating volume and BP
what does the counter current mechanism refer to
establishing a high conc gradient in the medulla
what does the counter current mehcnsim allow fro
eagles reabsorption of water from filtrate in the proximal tubule and collecting duct
in states of fluid loss how is the haemodynamic stability maintained though hormones? what do they do
- increased secretion of ADH = inserts more aquaporins into collecting duct = more absorption of water = conc urine with high osmolity
- renin : increase Na reabsorption and vasoconstriction
what does insensible loss refer to
- sweating
- faeces
- respiration
what is the best measure of fluid balance
taking a daily weight
What does the paraxial mesoderm go on to form?
The majority of the skeletal muscles, skeleton and dermis of the skin
What does the intermediate mesoderm go on to form?
The gonads, internal reproductive tract and kidneys
What does the lateral plate mesoderm go on to form?
The lining of the body cavities
When does kidney development begin?
Week 4
What are the three nephric structures?
- pronephros
- mesonephros
- metanephros
What is the pronephros?
Nephric structure denied from mesoderm in central region. This is a rudimental structure with no function and regresses.
What is the mesonephros?
A nephric structure in the lumbar region. It has a short period of function, but is remodelled and regresses.
What is the metanephros?
Forms the derivative kidney
Describe the formation of the pronephros
Occurs in the 4th week of development
- non-functional
- intermediate mesoderm in the cervical region condenses and reorganises
- forms a number of epithelial buds
- regresses around day 25
Describe the formation of the mesonephros
- week 4
- derived from the intermediate mesoderm in upper thoracic to the lumbar regions
- this is induced to epithiliase forming a solid duct.- mesonephric duct
- develops caudally and fuses with the walls of the cloaca at day 26
- canalisation comenses from the caudal end at day 26
What does canalisation of the nephric duct induce?
Formation of the mesonephric buds
Describe the formation of the mesonephric ducts
Tubules are formed in a craniocaudal fashion
Describe the formation of the Bowman’s capsule
The mesonephric tubules differentiate and
lengthen rapidly to form an S- shape and
Bowman’s capsule
Describe how the Glomerulus is formed
The tuft of the capillaries at the end of the elongated, differentiated mesonephric tubules forms the glomerulus
What forms the rudimentary excretory units?
The renal corpuscle
How do the mesonephric tubules regress?
6/7 Cranial-most tubules fuse with mesonephric duct • Function between weeks 6-10 to produce small amounts of urine • Mesonephric ducts then regress. • Male -> develop into reproductive structures • Female -> regress
What is the urogenital ridge?
Where gonadal development takes place (on the medial aspect)
Sometimes is referred to as the mesonephric ridge
When does the metanephros develop?
28 days
Describe the metanephros
- forms the definitive kidney
- has dual origin - the collecting and excretory portion
Describe the collecting portion of the metanephros
- collecting ducts
- major and minor calyces
- renal pelvis
- ureter
Describe the excretory portion of the metanephros?
- Bowman’s capsule
- Proximal consulted tubule
- Loop of Henle
- Distal convoluted tubule
What is the collecting portion of the metanephros called?
Uretic bud
What is the excretory portion of the metanephros called?
The metanephric mesenchyme
Describe the development of the metanephros
- Starts with the formation of the ureteric buds at the caudal end of the mesonephric duct
- by day 32 the steric buds penetrate the metanephric mesenchme
In short, what is the metanephros?
The collecting system
Describe development of the metanephros
The uteric bud penetrates the mesenchyme and branches
Renal pelvis -> Major calyces -> Minor calyces -> Collecting Tubules
What covers a newly formed collecting tubule of the metanephros?
A metanephric tissue cap
What does interaction between the tubule and the metanephric cap cause?
- Specific branching of the tubule
- Differentiation of cells in the metanephric cap to form renal vesicle
- Renal vesicle expands to form S-shape tubule and Bowman’s capsule
What makes up the nephron (a secretory unit)?
renal corpuscle
tubule
collecting tubule
Describe duplication of the Ureter
- premature bifurcation of the uteric bud
- bifurcation can be partial or complete
- bifid ureter
- ectopic ureter
- present in approximately 5% of the population
What causes renal agenesis?
early degeneration of ureteric bud or failed interaction between ureteric
bud and metanephric tissue cap
What are symptoms of renal agenesis?
- Generally asymptomatic
* Hypertrophy of remaining kidney
Why is bilateral renal agenesis not compatible with life?
Leads to Oligohydraminos (decreased volume amniotic fluid causing the fetus to present with
Potter sequence). Therefore, the foetus cannot develop respiratory muscles
What causes congenital cystic kidney disease?
- genetic factors
- Failure of induction between ureteric bud
and metanephric caps - Nephrons fail to develop and ureteric bud
fails to branch
Describe autosomal recessive congenital cystic kidney disease
- 1 in 5000 births
- cysts form in the collecting duct
Describe autosmal dominant congenital cystic kidney disease
- 1 in 500 to 1 in 1000 births
- Cysts form from all parts of the nephron
- Less progressive and usually presents in
adulthood
Describe relocation of the kidneys
• Kidneys develop in the pelvic region but reside in a more cranial position in the adult • ‘Ascent’ of the kidneys caused by growth and elongation of developing fetus • As the kidney ascends it establishes a new blood supply more cranially. The original lower vessels normally degenerate • Attain adult position by week 9
Describe horseshoe kidney
- occurs in 1/600 people
- inferior poles of kidney fuse
- resides in the lower lumbar region
- usually asymptomatic
Describe formation of the bladder
- In weeks 4-7, the cloaca divides into • Urogenital sinus • Anal canal - Separated by urorectal septum – mesoderm derivative
What are the three divisions of the urogenital sinus?
- Upper part: presumptive urinary bladder
- Pelvic part: Urethra
- Phallic part: Penile urethra (m) or vestibule (f)
With what structure is the bladder initially continuous with?
The allantois
What does the allantois obliterate to form?
The urachus that connects the apex of the bladder with the umbilicus in the adult
what is acute kidney injury also known as
acute renal failure
what is the general definition of acute kidney injury, include the time frame over which this occurs
rapid reduction in kidney function - occurs over hours or days
what rises and what normally decreases in acute kidney injury
creatinine
decreases in urine output (but not all forms usually have this association)
what are the risk factors for acute kidney injury
- > 75 yrs
- pre existing CKD
- previous episode of AKI
- debility and dementia
- heart failure
- liver disease
- diabetes
- hypotension
- sepsis
- hypovalemia
what are the pre renal causes for acute kidney injury
- sepsis
- hypotension
- hepatorenal syndrome
- renal artery syndrome
what are the post renal causes for acute kidney injury
- kidney stones
- prostatic hypertrophy
- tumours
- retroperitoneal fibrosis
what are the intrinsic causes for acute kidney injury
- prolonged pre-renal
- nephrotoxins
name some nephrotoxins
- gentamicin (used to treat bacterial infections)
- IV contrast
- NSAIDs
- rhabdomylosis
- haemoglobinuria
what is the most common form of acute kidney injury? what is this due to
ischaemia-reperfusion injury :
- due to a decrease in BP and reduction in perfusion
which position of the nephron does acute kidney injury normally occur
the proximal straight tubule - just after the proximal convoluted tubule
how does ischemia and reperfusion effect the epithelium of the proximal tubule in AKI
causes a loss of polarity of the brush border —> breakdown of the cellular membrane —> necrosis and apoptosis of the membrane cells —>leads to sloughing of viable and dead cells with luminal obstruction
normally after ischemia and reperfusion in AKI do we get repair of the membrane ? if so how?
yes we normally get complete repair
we get migration and differentiation of the viable cells leading to proliferation of the viable cells = reestablishing the polarity of the membrane
what 3 things occur if the membrane doesn’t fully recover ? what is the overall effect of this
- sustained loss of capillary density = decreased blood flow = hypertension
- immune response = activation of macrophages = inflammation
- tubular defect in proliferation = tubular apoptosis/senescene
= chronic fibrosis and scarring of tissue
what is the clinical presentation of AKI
- normally a silent disease
- few symptoms
- secondary to other illness
what kind of risk factors in patients lead us to suspect AKI
- hypovolaemia
- hypotension
- fever
- sepsis
- nausea, vomitting, diarrhoea
- high soma output
- haemorrhage : trauma
- burns
what investigations would we carry out for someone with AKI
- full blood count (high/low WBC with infection)
- U&Es and bicarbonate (good marker for previous kidney infection)
- C reactive protein
- Liver function tests
- calcium and phosphate
- immunological screen
- creatine kinase
- urinalysis
- ultrasound of renal tract within 24 hours if : obstruction suspected, rare cause suspected requiring biopsy
what do we check in a U&Es test in AKI
- electrolyte abnormalities (hyperkalaemia)
- uraemia
- raised creatinine
what levels are dangerous in CRP for AKI
when they are elevated = signal infection and inflammation
why do we test for calcium in AKI
high calcium signals myeloma (bone marrow cancer)
why do we do an immunological screen in AKI
vasculitis
why do we test for creaitine kinase in AKI
rhabdomyolysis
why would we do a urinalysis
- exclude infection
- blood and protein - vasculitis
how do we manage AKI
- depends on diagnosis
- majority of cases supportive
- treatment of underlying cause : sepsis, hypvolaemia
- stop/avoid toxins
- kidney replacement kidney
- rarer cases: refer to renal team, specific therapy
what does STOP AKI stand for
S- sepsis (treat)
T- toxins (avoid)
O- optimise BP/ volume status
P- prevent harm (identity cause, treat complications, review medication doses, review fluid prescription)
what is sepsis caused by
the way body responds to an infection - body overreacts to infection
what can sepsis lead to
increased capillary permeability:
- vasodilation and hypotension
- shock
- multiple organ failure
- CV collapse (Sevre hypotension)
- death
what is sepsis
life threatening organ dysfunction caused by dysregualted host reposes to infection
what is SOFA
Sepsis-related Organ failure assessment
what SOFA score is concerning
> 2
what are the factors of SOFA
- respiratory rate > 22/min
- altered mentation (mental state)
- systolic blood pressure <100mm Hg
what is septic shock
subset of sepsis
- profound circulatory, cellular and metabolic abnormalities
how does sepsis lead to multi organ failure
- endothelial dysfunction –> capillary leakage
- coagulopathy —> disseminated intravascular coagulation –> reduced tissue perfusion
- cellular dysfunction –> catabolic state –> reduced cellular energy consumption
- CV dysfunction –> L ventricular dilation –> hypotension
what can acute organ failure lead to
- acute lung injury
- CV instability (hypotension)
- AKI
- GI mucosal injury (translocation of bacteria from bowel to bloodstream)
- liver dysfunction
what are the risk factors for sepsis
- <1 year and >75 yrs
- very frail people
- recent trauma or surgery or invasive procedure
- impaired immunity due to illness or drugs (steroids, chemotherapy, immunosuppressants)
- indwelling lines/catheters
- IV drug misusers
- any breach of skin integrity : cuts, burns, blisters, skin infections
do people with sepsis always have specific symptoms
may have non-specific symptoms and non-localising presentations (eg. feeling v unwell)
what are the high risk criteria for sepsis
- respiratory rate : >25 breaths per min
- new need for oxygen :
- heart rate >130 beats per min
- systolic BP < 90
- not passed urine in previous 18 hours
- mottled or ashen appearance
- cyanosis of skin, lips or tongue
- non-blanching rash of skin
when should treatment for sepsis ideally begin
within the first hour
how do we treat for sepsis (think of the acronym)
BUFALO
- B: blood cultures
- U- urine output (monitor hourly - urine cultures, U & E)
- F: fluid resuscitation
- A- antibiotics (IV)
- Lactate measurement - from arterial or venous gas
- Oxygen - correct hypoxia
why do we prescribe resuscitation fluids in AKI or sepsis
to correct hypovolaemia - restore the BP and perfusion pressure to organs
what are the 2 types of hypokalaemia we can get
- true hypovolaemia
- relative hypovolaemia
what is true hypovolaemia ? how do we get it
when the rate of fluid loss of extra cellular fluid exceeds net intake eg: - haemorrhage - vomitting - diarrhoea
what is relative hypovolaemia ? how do we get it
when there is a decrease in the effective circulating volume
eg: sepsis
how do resuscitation fluids correct hypovolaemia
- restore the circulating volume by:
- rapidly expanding the intravascular space
- restoring the BP and organ perfusion
what are the main resuscitation fluids we use
crystalloids:
- 500mls Hartman’s solution
- 500mls 0.9% sodium chloride salt
if a patient presents with sepsis and is taking diuretics and ACEi do we stop them? how long for and why
yes we would stop them for a while due to fluid resuscitation management (to increase amount of fluid), however resume once patient has recovered
what is hyperkalemia? is it dangerous and why
high potassium
medical emergency - risk of cardiac arrest
what happens of an ECG of hyperkalaemia
- a tented T wave is presented (T wave is more raised and spiked)
- loss of the P wave
how do we manage hyperkalaemia
- calcium glutinate (shifts K+ into cell and protects cardiomyocytes)
- glucose and soluble insulin (facilitates uptake of glucose into the cell and thereby K+)
- stop drugs causing increased K+
- salbutamol nebulisers (push K+ intracellular)
in severe cases of hyperkalemia how would we mange it
kidney replacement therapy
if someone presents with pulmonary oedema how do we approach it (ie. treatment methods)
- sit up
- O2 high flow via reservoir mask
- high dose furosemide (loop diuretic)
- IV nitrates
- kidney replacement therapy
why would we give a high dose of furosemide to someone suffering from pulmonary oedema? in what case would we persist its use
- only if volume replete (v full)
- do not persist if unresponsive
what drugs are removed by the kidneys
- antibiotics : penicilin
- opioids : morphine
- metformin
- digoxin
what can an accumulation of penicillin cause
seizures
what can an accumulation of morphine lead to
- pinpoint pupils
- respiratory depression
what can an accumulation of metformin lead to
lactic acidosis
what can an accumulation of digoxin lead to
cardiac toxicity
what drugs can lead to nephrotoxity
- aminoglycosides: gentamicin
- NSAIDS (ibuprofen)
name indications where we would perform kidney replacement therapy
- hyperkalaemia unresponsive to medical therapy
- pulmonary oedema unrepsocive to medical therapy
- sevre acidaemia
- uraemia complications (increased urea)
name 2 uraemic complications
- encephalopathy (disease of the brain)
- pericarditis (friction rub= bleed = cardiac arrest)
what is the function of the Bowmans capsule
collects what is filtered through the glomerulus
what is the function of the proximal conciliated tubule
- reabsorbs 65% filtrate volume (glucose, AA, Na, Bicarb, water)
- secretes toxins (ammonia, creatinine, organic acids, some drugs)
- adjusts filtrate pH
what is the function of the descending loop of henle
water reabsorption
what is the function of the ascending loop of henle
reabsorbs Na/Cl
urea secreted
what is the function of the distal convolated tubule (hormone control)
- aldosterone: reabsorb Na and so Cl follows
- secrete K
- reabsorb Ca
- reabsorb bicarb and water
- synthesises bicarb
what is the function of the collecting duct
- ADH: reabsorb water
- reabsorb various ions (sodium, potassium, hydrogen ions, bicarb)
what does the glomerular filtration rate refer to
ultrafiltration of the plasma across the glomerulus into the urinary space
what is the glomerular filtration rate calculated from
- serum creatinine
- sex
- age
what is the normal value of GFR in healthy people
> 90mL/min/1.73m2
what is chronic kidney disease
- abnormalities of kidney structure or function which lead to decreased kidney function
is chronic kidney disease reversible
reversal is unlikely
what is the most common cause of CKD
diabetes
over what time frame does CKD present
present on at least 2 occasions > 3 months apart (long standing)
is eGFR of >60 normal? in what cases is it not
yes it is normal unless there are signs of kidney disease:
- urinary abnormalities
- electrolyte and other abnormalities due to tubular disorders
- structural abnormalities
- histological abnormalities
- genetic disease
- kidney transplantation
is CKD a silent disease
yes that’s why need to check the risk in that population (eg. black minority groups)
what are the causes of CKD
- diabetes (leads to diabetic nephropahty)
- glomerular disease (glomerulonephritis)
- obstruction
- inherited disorders
- renovascualr disease
- AKI
- reflux nephropathy
- interstitial disease
what inherited diseases can cause CKD
- autosomal dominant polycystic kidney disease
- Alport syndrome (x linked)
what are the complications of diabetes
- retinopathy
- neuropathy
- albuminuria/proteinuria
does glomerular disease effect one or both kidneys
immune mediated and effects both kidneys
what is the clinical presentation of glomerular disease
- nephrotic syndrome (leak large amounts of protein into urine)
- nephritic syndrome (inflammation of the kidneys)
what would we see in the urinalysis of glomerular disease
- haematuria
- proteinuria
what investigations would we carry out for someone with glomerular disease
- immunological investigations
- ultrasound
- kidney biopsy
what is the clinical presentation of nephrotic syndrome
- oedema
- hypoalbuminuria
- proteinuria
what is the clinical presentation of nephritic syndrome
- AKI
- haematuria
- proteinuria
- hypertension
what occurs in autosomal dominant polycystic kidney disease (ADPKD), include clinical presentation
- Development of multiple cysts
- hypertension
- cardiac abnormalities
- berry aneurysms
where do the cysts in ADPKD occur
kidneys
liver
pancreas
what chromosomes do ADPKD effect
chromosome 16 and 4
what’s the pahtophysiology associated with ADPKD
- Raised intra-glomerular pressure
- glomerulosclerosis
- tubulointersitial fibrosis
- loss of renal cortex
- shrunken kidneys
what is gloneruloscelrosis
expansion of glomerular mesangium and deposition of EC matrix
what happens in tubulointerstitial fibrosis
tubular atrophy
interstitial inflammatory cell infiltrate
deposition of EC matrix in intersitium
what are the signs and symptoms of CKD
silent disease
may not maifest until significant decrease of kidney function
what are the clinical manifestations of CKD
- Aches and pains
- loss of lean body mass
- reduced UO
- salt and water retention
- loss of appetite/ nausea
- sleep disturbance
- vomiting
- bleeding/bruising
what are the consequences of uraemia
- kidney failure (very high urea)
- pericarditis ( risk of cardiac tamponade- fluid increase in pericardium = press on heart)
- encephalopathy
- uraemia frost
what are the sings of encephalopathy
- reduced conscious level
- impaired cognition
- confusion
- coma
- seizures
what is uraemia frost
urea and urate deposits on the skin
which individuals are at high risk of CKD
- diabetes
- hypertension
- AKI
- CV disease
- structural renal tract disease
- multi system diseases with potential kidney involvement (eg.myeloma)
what are the initial screening of CKD
- blood eGFR
- urinalysis (blood/protein)
- BP
what further investigations would you carry out for CKD
- distinguish between AKI and CKD : baseline serum creatinine value and compare
- features to favour CKD:
anaemia
low calcium
high phosphate
elevated PTH
ultrasound appearances (scared/shrunken kidneys)
how would you manage CKD
- fluid balace (salt and water retention ) - loop diuretics
- hypocalcaemia (vit D analogues)
- tertiary hyperparathyroidism ( inhibit PTH secretion: calcimimetics)
- dose adjustments of drugs
- dietary advice : reduce K+ and phosphate
what specific therapy would we use for ADPKD
tolvaptan - vasopressin V2 receptor antagonists :
- inhibit cyst growth
- slow the decline of kidney function
before resulting to kidney replacement therapy what options do we have
- haemodialysis
- peritoneal dialysis (uses persons peritoneum to transfer dissolved substances)
- transplantation
what is the basic principle of the dialysis machines
blood with toxins moves into dialysis and toxins are removed from blood and put back into the blood
what kind of membrane inside the dialysis allows for toxins to be filtered out
semipermeable membrane
how many times a week and for how long do you carry out harm-dialysis
3 times a week for 3-4 hours
how Is peritoneal dialysis inserted
catheter is pushed through the skin and peritoneal membrane into the peritoneal space of the abdomen near the bladder - dialysis is carried out in this peritoneal space
hw does glucose concentration affect peritoneal dialysis
the higher the glucose concentration in the peritoneal dialyse the more ultrafiltration is achieved
when do you do an automated peritoneal dialysis
machine performs exchanges overnight
how does a continuous ambulatory Peritoneal dialysis work
manual exchange 3-4 times each day
1-3 L in each exchange
what are the (+) of haemodialysis
- less protein loss
- shorter treatment times
- social network at dialysis centre
- highly effeicnt small solute clearances
- no lag time to commence (PD requires several weeks before catheter can be used and training needed)
what are the (-) of haemodialysis
- hospital based
- scheduled treatment
- vascular access problems
- haemodynamic stress(blood moving from central to periphery)
- bleeding risk
- post dialysis : hypotension
- complications: infections, access failure
what are the (+) of peritoneal dialysis
- home based
- increased flexibility
- preservation of residual renal function
- less fluid restriction due to maintenance of residual urine output
- no anti-coagulation
what are the (-) of peritoneal dialysis
- dedicated space required for storage of equipment and fluid
- membrane failure - finale lifespan
- hyperglycaemia/ glucose load- disrupts diabetic control
- protein losses
- complications: hernias, peritonitis, sclerosing peritonitis (inflamtion of both parietal and visceral layers)
who is considered for a kidney transplant
- patients on dialysis or approaching dialysis
- patients must be fit to undergo surgery
describe the process fir a kidney transplant surgery
- a curved incision in the lower abdomen
- the kidneys vein is joined to the iliac vein which drains blood from the leg
- kidneys artery is joined to the iliac artery which supplies the leg with blood
what are the immediate post operative complications of a kidney transplant
- infections : bacterial pathogens (wound, urinary tract, respiratory tract)
- delayed kidney transplant functions: ischemia reperfusion injury
- rejection
there is administration of lifelong immunosuppressants in kidney transplant. what are the long term side effects of immunosupressents
- skin cancer (avoid direct sunlight)
- post transplanproliferative disorder (PTLD)
- infections : opportunistic infections, bacterial infections (UTI, pneumonia), viral infections (influenzas, covid)
what are the signs and symptoms of post transplant lymphoproliferative disorder
- weight loss
- fever
- lymphadenopathy
what is the main cause of death after a functioning kidney transplant
CVD
What are ACE inhibitors?
Prevent the conversion of angiotensin 1 to angiotensin 2 in the RAAS
How are the kidneys implicated in the RAAS?
Kidneys produce renin
which aids the conversion of angiotensiongen to angiotensin 1
What is the role of beta blockers?
Have an effect on the sympathetic system therefore inhibiting renin release
What does aldosterone stimulate?
Sodium uptake
Potassium excretion
Describe granular cells
contain renin
enter the Bowman’s capsule through afferent tubule
What stimulates renin secretion? (x4)
- Pressure changes in the afferent arteriole
- Sympathetic tone
- Macula densa (chloride and osmotic concentration)
- Local prostaglandin and NO release
What is the role of ACEi?
Inhibits the vasoconstrictive effect of angiotensin II
How do ACEi inhibit the vasoconstrictive effect of angiotensin II?
- dilates efferent arteriole
- reduces intra-glomerular pressure
- increases sodium and water excetretion
What are the indications for the use of ACEi?
- hypertension
- cardiac failure
- CKD (reduces the intra-renal pressure)
What are the side effects of ACEi?
- hypertension
- hyperkalaemia
- cough
Why may ACEi lead to hyperkalaemia?
They inhibit the effect of aldosterone
What are common examples of ACEi?
Ramipril and Lisinopril
What is an ARB?
Angiotensin Receptor Blocker
What is the role of ARBs?
Inhibits vasoconstrictive effect of angiotensin II on the receptor
How do ARBs inhibit the vasoconstrictive effect of angiotensin II on the receptor?
- dilates efferent arteriole
- reduces intra-glomerular pressure
- increases sodium and water excretion
What are the indications for ARBs?
- hypertension
- cardiac failure
- CKD
What are the side effects of ARBs?
Hypotension
Hyperkalaemia
What are examples of ARBs?
- valsartan
- irbesartan
What is an examples of an osmotic diuretic?
Mannitol
glucose in diabetes
Where do osmotic diuretics act?
The Bowman’s capsule
- they modify the contents of the filtrate
What is an example of a carbonic anhydrase inhibitor?
Acetazolamide
Where does acetazolamide act?
Before and after the loop of Henle
What are examples of loop diuretics?
Furosemide
Bumetamide
What do loop diuretics inhibit?
Uptake of:
- sodium
- potassium
- chloride
- water
What are the indications of loop diuretics?
- CKD
- Hypertension
- Cardiac failure
- Nephrotic syndrome
What are the side effects of loop diuretics?
- hypovalaemia
- hypokalaemia
What may hypovolaemia lead to?
AKI and cramps
What is the role of thiazides?
Inhibit sodium uptake so remove sodium and water
What are the indications for thiazide?
- CKD
- hypertension
- cardiac failure
- nephrotic sundrome
What are the side effects of thiazides?
hypovolaemia
hyponatraemia
What is the function of amiloride?
Inhibits sodium reabsorption in exchange for potassium
- removes sodium and water
What are the indications of amiloride?
prevents hypokalaemia
Why is amiloride descries as a weak diuretic?
It removes sodium and water
What are the side effects of amiloride?
hyperkalaemia
….. activate vitamin D
The kidneys
What form of vitamin D is given to those with CKD?
Vitamin D analogues that only require hydroxylation by the liver to the active form
What is an example of a vitamin D analogue?
Alpha calcidol
What are the side effects of vitamin D analogues?
- hypercalcaemia
- hyperphosphataemia
What do vitamin D analogues lead to in the gut?
Increased uptake of calcium and phosphate
Eryhtropoietin stimulates ….
erythropoiesis
Erythropoietin is produced by
cells in the intesitium of the kidney
Erythropoietin secretion is stimulated by
hypoxia
At what eGFR is erythropoietin required?
eGFR<15
How is erythropoietin administered?
subcutaneous injection
What are the side effects of erythropoietin?
- hypertension
- pure red cell aplasia
What are the consequences of reduced renal perfusion?
- reduced transglomerular pressure
- reduces GFR
What is the response of the kidney to reduced renal perfusion?
intra-renal activation of RAAS
- efferent arteriole vasoconstriction
- increases transglomerular pressure
- restores GFR
What is the effect of prostaglandins on the kidney?
- vasodilate the afferent arteriole
- maintain transglomerular pressure
What is the effect of NSAIDs on the kidney?
- inhibit prostoglanins leads to - vasoconstriction of afferent arteriole - decrease transglomerular pressure - decreased GFR
What maintains transglomerular pressure and GFR?
- prostoglandins of the afferent arteriole
- angiotensin II on the efferent arteriole
Why do ACEi and ARBs lead to decreased transglomerular pressure and reduced GFR?
They inhibit efferent arteriolar vasoconstriction
All penicillins except Flucoxacillin are removed by the …
kidneys
Opiod analgesics are removed by …
the kidneys
Opiates with minimal renal excretion are
- fetanyl
- oxycodone
- hydromorphone
What is digoxin used for?
Antiarrythmic drug
- eg atrial fibrilation
Accumulation of digoxin in the kidneys leads to…
- bradycardia
- visual disturbances
- mental confusion
- aggrevation of hyperkalaemia
Metformin is removed by
the kidneys
Accumulation of metformin in the kidneys leads to
hypoglucaemia
lactic acidosis
Metformin use should be avoided if
GFR < 30ml/min
What herbal preparations may effect the kidneys?
aristocholic acid eg in cat’s claw
What characterises nephrotic syndrome?
proteinuria
- therefore hypoalbuminaemia and oedema
hypercholestolaemia
What protein is predominantly lost in proteinurea?
Albumin
What are the signs and symptoms of nephrotic syndrome?
- severe swelling, particularly around the ankles
- foamy urine due to proteinuria
- weight gain due to fluid retention
- fatigue
- loss of appetite
What is the glomerular filtration barrier?
3 layered structure
facilitates flow of plasma, water and small molecules while restricting the flow of large plasma proteins
The 3 layers of the glomerular filtration barrier (GFB) are …
- endothelium
- glomerular basement membrane
- podocyte
What is the glomerular basement membrane?
the extracellular matrix component of the selectively permeable glomerular filtration barrier (GFB) that separates the vasculature from the urinary space
The GFB is synthesised by
glomerular endothelial cells and the podocytes (epithelial cells) that sit on the opposite side of the GBM within the urinary space
The GFB has a … charge
net negative charge
Why is the negative charge of the GFB significant?
It acts as a filtration barrier to plasma albumin which is negatively charged
Why is the GFB compromised in nephrotic syndrome?
there is injury to the epithelial foot process
- podocyte fusion and collapse
- reorganisation of the actin cytoskeleton
means that albumin can pass through
What medical conditions are causes of nephrotic syndrome?
- diabetes
- minimal change disease (children)
- membranous nephropathy
- focal segmental glomerulosclerosis
- systemic lupus erythematosis
- amyloid
What infections cause nephrotic syndrome?
HIV
Hep B
Hep C
Malaria
What medications cause nephrotic syndrome?
NSAIDs
What genetic variant can the disparity in prevalence of diabetes be attributed to?
APOL1
How is nephrotic syndrome treated?
specific therapy depending on the cause
- diabetes = management
- minimal change disease/membranous nephropathy/fsgs = steroids
- amyloid= chemotherapy
