Kidney Stones Flashcards
What brought Mr Stanworth in?
Fatigue
He thought it could be related to thyroid
What were his abnormal test results?
Kidney function
High serum creatinine
High urine protein
Higher HBA1c
What does the doctor request?
Referral to kidney clinic
Ultrasound of kidney
Write to diabetes specialist
What long term condition does Mr Stnaworth have?
Type 2 diabetes
What is important in Mr Stanworth’s management?
Blood pressure control
Blood sugar control
What is diabetic nephropathy?
Kidney damage caused by diabetes
What is diabetic nephropathy also known as?
Kidney disease
What proportion of those with diabetes need treatment for kidney disease?
1 in 5
What causes kidney disease?
High blood glucose damages the small blood vessels and filters in the kidney
High blood pressure also does this
Causes leaks and abnormal amounts of protein leaves body via urine
What are the symptoms of kidney disease?
Swollen ankles, feet and hands Blood in urine Fatigue Shortness of breath Nausea
How can the risk of kidney disease be reduced?
Keep blood sugar within target range Keep blood pressure down Stop smoking Eat healthily and keep active Go to all medical appointments
What are the tests for kidney disease?
Both included in 15 healthcare essentials Urine test (ACR) Blood test (eGFR)
What is the urine test called?
Albumin: creatinine ratio
Looks for signs that protein is leaking into urine
What does the blood test look for?
Tests for creatinine
Used to estimate glomerular filtration rate
How long does it take to receive blood test results?
A week
How is kidney disease treated?
High blood pressure managed by: ace inhibitors or a ARBs
Possible advice to avoid certain foods
How is late stage kidney disease treated?
Kidney transplant
Dialysis
What support is available to those with kidney disease?
Diabetes team National kidney Federation British kidney patient Association Diabetes.org helpline Kidney research UK
What is the glomerulus?
Bowl of capillaries surrounded by the Bowmans capsule into which urine is filtered
What does the filtration barrier consist of?
Endothelial cells is glomerular capillaries
Glomerular basement membrane
Epithelial cells of Bowmans capsule (podocytes)
What are Perforations in the glomerular capillaries endothelium called?
Fenestra
How big are fenestrae?
70no
What is the role of these pores?
Do not restrict the movement of water and proteins or large molecules
But instead limit the filtration of cellular components e.g. RBCs
What surrounds the luminal surface of the endothelial cells?
Glycocalyx
What does glycocalyx consist of?
Negatively charged glycosaminoglycan is which function to hinder the diffusion of negatively charged molecules
What is the basement membrane made up of?
Mainly type IVcollagen
Heparan sulphate proteoglycans
Lamina
What are the three layers of the glomerular basement membrane?
And inner layer: lamina rara interna
A thick layer: lamina densa
An outer dense layer: lamina rara externa
What are podocyte?
Specialised epithelial cells of Bowmans capsule which form the visceral layer of the capsule
What projects from the podocytes?
Foot like processes which interdigitate to form filtration slits
The filtration slits abridged by a thin diaphragm Which has very small paws preventing large molecules from crossing
What is around the podocytes?
Negatively charged glycoproteins
Restrict filtration of large and anions
What percentage of nephrotic syndrome is minimal change glomerulonephritis?
10 to 25%
What triad of symptoms is experienced in a nephrotic syndrome?
Proteinuria
Hypoalbuminaemia
Oedema
How do the glomeruli appear under a light microscope in minimal change disease?
Normal
How do the glomeruli appear under an electron microscope in minimal change disease?
Diffuse effacement of the foot processes of podocyte
Microvillous change seen on the podocytes
What is the pathology a minimal change disease?
Uncertain and considered idiopathic
Thought to be due to a T-cell derived factor
What do patients with minimal change disease often respond well to?
Steroid therapy
Symptoms may relapse if the patient comes of steroid therapy
Some patients become steroid dependent but most do not progress to chronic renal failure
Those that do usually have focal segmental glomerulosclerosis as well
What is Alport syndrome?
Genetic disease characterised by progressive chronic kidney disease
So the symptoms of Alport syndrome?
Heamateria
Sensorineural deafness
Ocular abnormalities
What is the genetic mutation and inheritance of Alport syndrome?
In majority of patients inheritance is X-linked
With mutations of the gene coding for alpha five chain of type 4 collagen
What does the mutation in Alport syndrome result in?
Thinning of the lamina densa
Multilayering produces a basket weave appearance
What occurs in the later stages of Alport syndrome?
Glomerulosclerosis
Interstitial fibrosis
Tubular atrophy
What is the treatment for Alport syndrome?
No definitive treatment
But ACE Inhibitors are given to reduce proteinuria and progression of renal disease and also to control hypertension
What is the renin angiotensin aldosterone system?
Call moon system within the body that is essential for the regulation of blood pressure and fluid balance
What three hormones comprise the RAAS system?
Renin
Angiotensin II
Aldosterone
What is the system primarily regulated by?
Rate of renal blood flow
What is the first stage of the system?
Release of renin From the granular cells of the renal juxtaglomerular apparatus
What three factors trigger renin release?
Reduced sodium delivery to the distal convoluted tubule detected by macula densa cells
Reduced perfusion pressure in the kidney detected by Barrow receptors in the afferent arteriole
Sympathetic stimulation of the JGA via beta one adrenoreceptors
What is the release of Renin inhibited by?
Atrial naturetic peptide which is released by stretched atria in response to increased blood pressure
What is angiotensinogen?
Precursor protein produced in the liver and cleaved by renin to form angiotensin I
How is angiotensin I converted to angiotensin II?
Angiotensin converting enzyme
This conversion occurs mainly in the lungs where ACE is produced by vascular endothelial cells
How does angiotensin II exert its action?
Binds to various receptors throughout the body
Binds to one of 2G protein coupled receptors, AT1 and AT2
Most actions occur via the AT1 receptor
What is the action of angiotensin II on arterioles?
Vasoconstriction
What is the action of angiotensin II on the kidney?
Stimulates sodium reabsorption
What is the effect of angiotensin II on the sympathetic nervous system?
Increased release of noradrenaline
What is the effect of angiotensin II on the adrenal cortex?
Stimulates release of aldosterone
What is the effect of angiotensin II on the hypothalamus?
Increases thirst sensation and stimulates antidiuretic hormone release
What are the cardiovascular effects of angiotensin II?
Acts on AT1 receptors
Signalling occurs via Gq protein to activate phospholipids C
Increases intracellular calcium
Net effect: Increase in total peripheral resistance and consequently blood pressure
What are the neural effects of angiotensin II?
Thirst and secretion of ADH from the posterior pituitary gland increases circulating volume and therefore blood pressure
What is the effect of noradrenaline on the system?
Increase in cardiac output
Vasoconstriction of arterioles
Release of renin
How is vasoconstriction achieved in the renal artery and afferent arteriole?
Voltage gated calcium channels open and allow an influx of calcium ions
How is vasoconstriction achieved in the efferent arteriole?
Activation of AT1 receptor?
What effect does angiotensin II have on mesangial cells?
Contraction, leading to decreased filtration area
Achieved by activation of GQ receptors and opening of voltage gated calcium channels
How does angiotensin II increase sodium reabsorption in the proximal convoluted tubule?
Increased sodium hydrogen antiporter activity
Adjustment of the starling forces in peritubular capillaries to increase paracellular reabsorption
What does tubuloglomerular feedback do?
Helps to maintain a stable glomerular filtration rate
The release locally of prostaglandins which results in a preferential vasodilation to the afferent arterial is vital to this process
What is aldosterone and where is it released from?
It is a mineralocorticoid released from the Zona glomerulosa of the adrenal cortex
What cells does aldosterone act on?
Principal cells of the collecting ducts in the nephron
Increases the expression of apical epithelial sodium channels to reabsorbed urinary sodium
Activity of the basolateral sodium potassium ATPase is increased
What can increase levels of aldosterone produce with regards to potassium?
Reduce levels of potassium in the blood
What are ACE inhibitors?
Class a drug typically used in the treatment of hypertension and heart failure
Some examples of ace inhibitors
Ramipril
Lisinipril
Enalapril
What do ace inhibitors do?
Inhibit the action of angiotensin converting enzyme
Reduce levels of angiotensin II within the body
What is the physiological effects of ace inhibitors?
Decreased arteriolar resistance
Decreased arteriolar vasoconstriction
Decreased cardiac output
Reduced potassium excretion in the kidneys
What are the side-effects of ACE inhibitors?
Dry cough Hyperkalaemia Headache Dizziness Fatigue Renal impairment Rarely Angioedema
What are the two most important prognostic factors in chronic kidney disease?
Hypertension
Proteinuria
How do you ACE inhibitors reduce proteinuria?
Inhibition of the preferential vasoconstriction that occurs in the efferent arterial in the glomerulus
Thus reducing GFR and reducing urinary protein excretion
In which patients should ace inhibitors be with held from or used with caution?
Bilateral renal artery stenosis
Acute kidney injury
What is the function of the kidney?
Reabsorption
Secretion
Filtration
Excretion
What is the functional unit of the kidney?
Nephron
What makes up the nephron?
Afferent arteriole Glomerulus Efferent arteriole PCT Loop of Henle DCT Collecting duct
What is initial filtration dependent on?
Size and charge
How is the nephron smart?
Salvaging on the basis of requirement
Secretion according to need
What are the main features of creatinine?
Non protein molecule
Filtered freely
Not reabsorbed
High serum levels shows problems with filtration
By what mechanism does proteinuria occur?
Proteins filtered through glomerulus with smaller ones passing through easily
Renal epithelial cells reabsorb proteins via endocytosis particularly in PCT
Normally all filtred proteins are reabsorbed
What is the exception?
Secreted proteins e.g. Uromodulin
What is overflow proteinuria?
Rhabdomyolysis: rapid breakdown of skeletal muscle
Results in muscle constituents being released to blood stream e.g. myoglobin
OR excess Haemoglobin due to excessive haemolysis
Excess of blood in bloodstream
Only so much reabsorption so protein is lost in urine
What is glomerular proteinuria?
Diabetic nephropathy
More protein let through
-Secondary glomeruopathy (secondary to disease or drug)
- Primary glomerulopathy (intrinsic)
What is the difference between haemoglobinuria and heamateria?
Free Haemoglobin vs. Bleeding from the urinary the tract itself also has intact red blood cells
What type of protein is predominantly lost in glomerular proteinuria?
Albumin
Intermediate size protein roughly same size as glomerular pore
Flexible
What are the main features of tubular protein area?
Acute tubulointerstitialnephritis
Can be acute or chronic
Acute- nephrotoxic drugs
Which for drugs are the most common cause of acute kidney injury in hospitalised patients?
Amino glycosides
Contrast
NSAIDS
ACE inhibitors
Which of these mechanisms do you think is capable of the biggest protein loss?
All of them
Which arterioles hyperglycaemia particularly affect?
Efferent
Which system does hyperglycaemia directly activate?
RAA
What does afferent arteriolar narrowing do?
Increases upstream pressure in the glomerulus
What does hypertension cause in the glomerulus?
Increased flow through the afferent arteriole, further increasing glomerulal pressure
What with the glomerulus usually be protected by?
Auto regulation and afferent arteriolar constriction
But this feedback mechanism is altered in diabetes
Why does diabetes increase sodium reabsorption?
Proximal tubule is work hard to reabsorbed excess glucose increased sodium reabsorption because sodium is Co transported with glucose
What does low-sodium uptake by macula densa cells cause?
Less stimulation of afferent arteriole vasoconstriction
What happens to patients early and diabetic nephropathy?
Patients have increased filtration rates
What is glomerulosclerosis?
Excessive extracellular matrix that leads to the hardening and scarring of the glomerulus
Results in reduced capacity for filtration
What intrinsic changes to the basement membrane are seen in those with diabetes?
It becomes thickened and structural changes means it also becomes leaky
What is nephrin?
Key protein component of podocytes
What are the most common causes of chronic kidney disease in the western world?
Diabetes
Hypertension
Glomerulonephritis
What happens in the kidneys when around 50% of nephrons are damaged regardless of pathophysiology?
Adaptive hyperfiltration- blood flow shunted to functioning nephrons and away from damaged ones
What does adaptive hyperfiltration lead to in originally healthy nephrons?
Glomerulosclerosis
Ischaemic injury
Loss of filtration
Nephron loss
What’s the best way to monitor or screen for proteinuria in diabetes?
Albumin: creatinine
Ratio of urine sample
What is the issue with a urine dip stick test?
Detects albumin
But poor sensitive
Might miss cases
Does not detect some proteins e.g. myoglobin
How much albumin lost today is normal?
Less than 30mg a day
Usually 5-10mg a day
What is the issue with a 24 hour urine test?
Relied on patient to accurately collect all urine
Impractical
Often not collected accurately
Total protein should be less than 150mg a day
What is the issue with random albumin concentration?
Unreliable
Depends on urinary concentration
Depends on patients hydration
Why is in albumin creatinine ratio of urine sample used?
Account for differences in urine concentration
Provides reasonable estimate of protein loss
Used in diabetes: greater sensitivity
Why do you check for proteinuria in diabetes?
Cardiovascular risk
Identification and early diagnosis
Often a sign of damage in other areas and can predict those that are more likely to progress to chronic kidney disease
What is microalbumiuria?
Albumin loss between 30-300mg a day
Predictive and prongnostic marker of CKD
What is macroalbuminuria?
Greater than 300mg lost a day
Now moderate and severe are the proffered terms
What is GFR?
Glomerular filtration rate
How can GFR be estimated?
What volume of fluid is filtered from the glomerular capillaries to the bowman capsule per unit time
Proportional to clearance of a certain substances
Why is creatinine used?
Freely filtered
Not reabsorbed
Ideally not secreted but a little it (5-10%)
Considered roughly proportional to GFR
What is clearance equal to?
Urinary [substance] x urine production rate divided by plasma [substance]
What is done clinically to estimate GFR?
Evidence Based formula is that you serum creatinine without need for urinary creatinine
More practical
What is the most commonly used formula?
MDRD formula
Origin: the modification of diet in renal disease study
Tracer injected IV (isotopic]
What is considered in the MDRD formula?
Age
Ethnicity
Gender
Why are these demographic data important?
Different serum creatinine depends on amount produced which is higher with increasing creatinine
Also depends on dietary protein consumption
In who should this formula be used carefully?
High protein diets Extremes of weight Amputees Body builders Muscle wasting conditions Pregnant women
What do you aim to catch early?
Albuminuria
What are the markers of chronic kidney disease?
Albuminorrhoea Electrolyte abnormalities Abnormal abnormalities on histology Structural abnormalities Kidney transplantation
What else must be considered when using Creatine to estimate GFR?
When serum creatinine is unstable
E.g. acute kidney injury
What factors in an acutely unwell patient might impact the serum creatinine?
Drugs Trauma Malnutrition Muscle wasting Sepsis
Why is it not reliable in pregnant lady?
Filtration rate increases
GFR estimate unreliable
Why is it not reliable and should be used with caution in those with end stage kidney disease?
In end stage kidney failure
As GFR falls the proportion of Creatine secreted increases and the amount actually filtered decreases
What is Mr. Stanworth’s diagnosis?
3A A2 CKD
What medication should Mr. Stanworth be started on?
Ramipril- ACE inhibitors reduced glomerular pressure
Atorvastatin
Insulin
Target the modifiable risk factors
Hypertension
dyslipidepia
Hyperglycaemia
What causes symptoms of CKD?
Decreased excretion
Decreased biosynthesis
Altered metabolism
Main features of decreased excretion
Increased sodium and water: volume overload Hyperkalemia: increased potassium Increased H+: metabolic acidosis Increased urea Increased uric acid: gout Increased phosphates: renal bone disease
Main features of decreased biosynthesis
Anaemia due to reduced erythropoietin synthesis
Normocytic, normochromic
Vitamin D decreasing- renal bone disease
Main features of altered metabolism
Abnormal lipid metabolism
Sex hormones: sexual dysfunction
What is released By the kidneys to aid absorption?
Vitamin D
What do the kidneys aid absorption of?
Calcium
What senses a decrease in the absorption of this molecule?
Parathyroid gland
What is used to hydrolyse stores of this molecule?
Parathyroid hormone
Where is this molecule stored?
Bone
What is molecule Y?
Phosphate
What is molecule Z?
FGF23
Bone derived hormone
Elevated in CKD
Decreases reabsorption and increases secretion of phosphate
What is the likely progression for Mr Stanworth’s chronic kidney disease?
He has CKD stage two with eGFR of 61
Has moderate albuminuria
Expect to progress to 3a within 2 years
3b within 10 years
Improvement in first year or so due to drug interventions
What is the take home message?
Early detection is key
What does the general management for CKD involve?
Treatments of reversible causes
Preventing or slowing the progression
Treatments of complications of renal failure
Adjusting drug doses when appropriate for the level of eGFR
Identification and adequate prep of patient in whom renal replacement therapy will be required
What are the reversible causes of renal failure?
Decreased renal perfusion
Administration of nephrotoxic drugs
Urinary tract obstruction
What causes decreased renal perfusion?
Hypovolemia
Hypotension
Infection
Administration of drugs
What drugs can interfere with creatinine secretion and the creatinine assay?
Trimethoprim (UTI antibiotic)
How do drugs interfere with creatinine assays?
Does not change glomerular filtration rate
may reuse tin increased serum creatinine
Why may a urinary tract infection always be considered?
Inhibits the flow of urine
What can cause a UTI?
prostate enlargement
kidney stone
ureteric scars
strictures
What is hydronephrosis?
Where the kidney is swollen due to inability to drain properly
What therapeutic modalities can be used to offer renal protection?
Protein restriction
Stopping smoking
Treatment of chronic metabolic acidosis
Control of blood glucose
How do you treat volume overload?
Combination of dietary sodium restriction
Diuretic therapy
In which patients is hyperkalaemia seen?
Oliguiric patients
High-potassium diet
Increased tissue breakdown
Hypoaldosteronism
How is metabolic acidosis treated?
Bicarbonate supplementation
What is phosphate retention related to?
Secondary hyperparathyroidism
What changes in bone structure are seen in progressive CKD?
osteitis fibrosa
osteomalacia
dynamic bone disease
How are the bone disorders treated?
dietary phosphate restriction
administration of oral phosphate binders
calcitriol
What percentage of CKD patients have hypertension?
80-85%
What are the big six?
Eating healthily Regular exercise Give up smoking Reduce alcohol intake Keep blood pressure down Control diabetes
