ILO WEEK 7 & 8 Flashcards
Renal
Give an account of the role of the kidneys in controlling the volume of extracellular fluid, metabolic waste removal and electrolyte homeostasis
The role of the kidney is to:
- Remove metabolic waste from the extracellular fluid (urea, acids)
- Controlling the volume of extracellular fluid ( close link to blood pressure)
- Maintaining optimal concentration of vital solutes in the extracellular fluid (Na, K, Ca, Mg, Cl, Phos)
- A few other functions have evolved as a result of kidneys unique physiology
Controls the volume by ADH and aqua poring; rest of the water follows sodium!
Metabolic waste; things reabsorbed and actively excreted from the body;
Loop of Henle
Describe the composition of the nephron and explain the function of each component
- Glomerulus -> ultrafiltration; podocytes; leaky capillaries; pressure difference
- Proximal convoluted tubule -> active reabsorption; most occurs here-> all glucose and amino acids; lots of electrolytes and water
- Loop of Henle -> concentration; creating environment for water reabsorption ( descending water only; ascending electrolytes only) Sodium potassium chloride channels
- Distal convoluted tubule -> small reabsorption only; same as in proximal but just adjusting
- Collecting duct; collecting all; ADH water reabsorption
Understand the other main functions of the kidneys, including activation of vitamin D, toxin metabolism and regulation of erythropoietin
- Vit D activation -> last stage of Vit D activation
- Regulation of erythropoein -> makes erythropoein -> making red blood cells
- Blood pressure regulation; macula densa; renin;angiotensin; aldosterone
- Toxin metabolism
Some of toxin metabolism occurs in the kidney ( medicines; degoxin)
Juxta-glomerular apparatus and blood flow
Juxta-glomerular apparatus:
Maintains GFR in face of increases or decreases in blood flow to the kidney
Macula densa - senses tubular flow; next to glomerulus
Increases tubular flow:
Sensed by macula densa
Macula densa produces adenosine -> afferent arteriolar constriction
Reduced tubular flow:
Sensed by macula densa; reduction in flow
Granular cells produce renin (green)
Describe the common causes and classification of kidney disease
Defined by reduced eGFR and detection and qualification of urine protein +/- blood
Once defined a combination of history, examination and investigation is employed to identify aetiology
AKI (Acute Kidney Injury); CKD (Chronic Kidney Disease)
Common causes:
- Ineffective blood supply (reduced effective plasma volume or narrowed renal arteries) mostly AKI
- Glomerular diseases
- Tubulo-interstitial diseases
- Obstructive uropathy most AKI
- For CKD -> Following acute kidney injury
Oliguria
Warning od impending acute tubular necrosis
List what is measured by semiquantitative urinalysis
- Inspection
- Dipstick testing
Microscopy and quantification of detected protein - Depending on clinical situation- urine biochemistry (sodium, potassium, chloride, urea, osmolality)
Check:
- Protein/Albumin
- Haem
- pH
- Ketones
- Glucose
- Bilirubin
- Leucocyte
- Nitrites
Blood:
- visible haematuria
- non-visible (seen with a microscope)
Protein:
Measuring, need 24h sample
No normal values for electrolytes
How proteinuria and Haematuria are quantified
Blood:
- visible haematuria
- non-visible (seen with a microscope)
Protein:
Measuring, need 24h sample
need a ratio with creatine
Identify patients with kidney injury by eGFR, serum creatine, dipstick urinanalysis and urine quantification
- > eGFR <60 ml/min
- > Rise in serum creatine within the eGFR> 60mL/min range
- > Anion gap
- > Blood and proteins
Management of Chronic Kidney Disease
- > Dialysis
- > Kidney transplant
- > Increased cardiovascular risk
Describe the various methods available to image the kidneys and bladder and understand the risks associated with some of these methods
- Plain X-ray
(useful for radio-opaque stones - Ultrasound
(no radiation; gains information about kidney size; shape; location; obstruction and renal blood flow) - CT
( Useful for trauma, stone, tumour, infection) (popular)
Contrast enhanced imaging Blood supply and neighbouring structures; (IV iodinated contrast -> potentially methatoxic)
NEED to weight up benefits and potential nephrotoxicity; sometimes really needed
- MRI
Soft tissue evaluation; contrast can be toxic - Radioisotope scanning
tracer needed
information on: structure; perfusion; excretion; differential renal function
Understand how kidney stones/ crystals form, and the different types that exist
Crystals too much solute for the solution:
- calcium; Oxalate; Urate; Cysteine
Not enough solution: filtrate, urine
They form in urinary space
Classification: By location: - kidney/ nephrolithiasis - ureter/ ureterolithiasis - bladder/ cystolithiasis
By composition:
- calcium- phosphate/ calcium-oxalate
- urate/ cysteine/ struvite
Risk factors:
- male; 50% have a genetic component; positive family history
rise in obesity+ metabolic syndrome (DM/ HBP) have caused an increase in uric acid stones
Composition: - Calcium containing (80%) Calcium OXalate; Calcium Phosphate Magnesioum ammonium Phosphate Uric Acid; Cysteine; Mixed stones
HIGH SOLUTE STATES? LOW PREVENTER STATES
Understand the role of serum/ urine biochemistry and imaging in diagnosing kidney stones
pH Urine -> may be helpful in guiding diagnosis/ treatment:
Calcium stones pH >7.0
Struvite pH >7.0
Uric acid + cystine pH <6.0
High solute states: High calcium; High Oxalate/ Urate/ Cysteine/ Pro-calculi
CITRATE IS PROTECTIVE
Serum biochemistry tests: calcium, Phosphate, PTH, Urate, Bicarbonate
Discuss the common treatments for kidney stones
<2 cm expectant management or offer extracorporeal shock wave lithiotripsy
>2 cm or multiple stones -> expectant management ultrasonic litrotripsy
Large branched stones may require pul and eswl
Cysteine stones pul or open nephrolithotomy
Stones in ureter:
- small have a good chance of paddage
- allow time to pass
- lower ureter - ureteroscopic stone removal
- mid-upper ureter eswl
- large stones -> >7mm eswl; ureteroscopic stone fragmentation
- open surgery
IN ALL increase fluid! In some change the diet: (low oxalate; reduce protein/ sodium)
Citrate inhibitor of stone formation; can be increased by low Na diet
Struvite (Magnesium Ammonium Phosphate) -> Debulk where possible; Aggressive treatment of UTI (made by worms)
Functions of the kidney and consequence of failure in thees
- Excretion small solutes -> consequence -> increased plasma concentration (e.g. urea, creatine)
- Excretion of drugs -> drug toxicity
(Done by filtration and tubular secretion) - Salt & water balance -> extracellular fluid overload or depletion
Blood pressure control -> Hypertension
( Pressure natriuresis renin/angiotensin system, ADH, countercurrent mechanism, ANP/ BNP) - Electrolyte balance -> Hyperkalaemia, hypokalaemia
- Acid base balance -> Metabolic acidosis
( Filtration then tubular cell membrane ‘pumps’) - Erythropoein -> Anaemia
- Vit D activation -> Hypocalcaemia and secondary hyperparathytoidis
Describe how the nephron controls excretion of sodium and potassium
Potassium is mostly intracellular
Sodium and Chloride are in the interstitium
The kidney can only alter what it has filtered
Afferent arteriole Central nervous system
Efferent -> Angiotensin II constricting
+ ALL other mechanisms that control filtration
Then tubular reabsorption (active via channels) (passive down conc. gradient or osmotic gradient)
Tubular secretion -> In distal conv. tubule
Excretion = (Filtration - Reabsorption) + Secretion
Explain how the kidney controls water reabsorption and secretion
Water follows sodium
Lots reabsorbed in the proximal conv. tubule;
In the loop of Henle; water leaved in the descending limb
The in distal and collecting duct; special system for further water reabsorption ADH; AQUAPORINS -> going down conc. gradient due to the loop of HENLE
Describe how the countercurrent multiplier system concentrates filtrate in the loop of Henle
Descending -> only water permeable passive process
Ascending -> sodium, potassium, chloride permeable; Osmolality highest at the bottom; then electrolytes lost as it goes up -. Ends up being diluted at the top? all electrolytes are outside
Understand how the countercurrent mechanism functions in the Vasa Recta
Vasa Recta is the vessel that appears in the juxtamedullary nephrons;
They flow in the opposite direction to the loop of Henle; but alongside it. It does not wash away the gradient as it flows in the opposite direction; It moves water into the ascending and electrolytes into the descending loop
Understand the channels involved in electrolyte transport
Na+K+ ATPase and NaH antiporter (in PCT)
NKCC2 (Thick Ascending Loop of Henle)
NCC (DCT) (Na+ 2Cl-)
Aquaporins (Collecting Duct)
ENaCl (Cortical collecting duct)
IS THERE MORE?
List the mail hormones involved in regulating renal function and understand how they act
Angiotensin II; Aldosterone; Renin -> Blood pressure; Contract on the afferent and efferent arterioles to go increase the flow (Maintain)
ADH and aquaporins -> open channels to allow passive passage of water out of the tubule
Understand the mechanism involved in renal excretion of drugs
Drug elimination:
- Glomerular filtration; doses should be reduced if less filtration
- Tubular secretion
- Diffusion (non-ionic) - related to pH of urine/pKa of the drug ( important in aspirin)
- Protein-blinding ( in low serum albumin; more free and being filtered free fraction - rate of filtration
Describe how impaired kidney function has an effect on drug metabolism and clearance
Problems:
- Toxicity
- Ineffective treatment
Relevant factors:
- Impaired drug absorption
- Impaired elimination
- Effect of renal dysfunction on hepatic drug metabolism
- Increased tissue sensitivity
- Protein binding
Impaired renal function: Altered pharmacokinetics: - decreased elimination - decreased protein binding - ALtered drug effect Worsening of the existing condition Enhancement of adverse effects
Explain the dose adjustment options necessary in patients with compromised kidneys
Decreased elimination:
- Modify dose or monitor drug concentration
- decreased dose -> decreased peak concentration
- Increased dose interval -> decrease trough concentration (less exposure)
Both -> more uniform serum concentration
GOOD EXAMPLE: Gentamicin
