Renal Flashcards
How many nephrons in each kidney?
800,000 to 1,200,000
What forms the filtration slits in the renal corpuscle?
Podocytes - pedicles project.
What are the two capillary beds of the nephron?
Glomerular, peritubular
What % of cardiac output do the kidneys receive?
20%
What is the normal filtration rate of the kidneys?
180L/day
How much water is excreted in urine under normal conditions?
1.5L
Functions of the kidney? (6)
Volume/BP, concentration, pH, metabolic, excretory, endocrine
Simply, how do the kidneys control blood volume?
Excretion or retention of fluid
What ions do kidneys maintain the concentration of? (7)
Sodium (Na+), potassium (K+), chloride (Cl-), magnesium (Mg2+), hydrogen (H+), bicarbonate (HCO3+), calcium (Ca2+)
Which ions are regulated in the kidney to control blood pH?
H+, acidic. HCO3+, alkalotic.
What role do the kidneys play in metabolism? (2)
A small amount of gluconeogenesis, activate vitamin D from 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D
What endocrine function do the kidneys serve? (2)
Production of erythropoietin, renin production (RAAS system)
What excretory function do the kidneys serve? (3)
Excreting - metabolic waste inc. urea & creatinine, water-soluble drugs, toxins
What 3 types of balance do the kidneys maintain?
Acid-base, fluid, electrolyte
What does the GFR stand for and what does it mean?
Glomerular filtration pressure - net filtration pressure across glomerular capillaries.
What blood vessels control blood flow & hydrostatic pressure in the intervening glomerular capillary?
Afferent & efferent arterioles.
Increased resistance in the afferent arteriole has what effect?
Lower renal blood flow, lower net ultrafiltration pressure
Increased resistance in the efferent arteriole has what effect?
Lower renal blood flow, higher net ultrafiltration pressure
Sympathetic stimulation/norepinephrine release has what effect on the renal arterioles?
Vasoconstriction of afferent AND efferent arterioles - resistance in both rises, generally decreasing RBF & GFR.
Generally, what effect does angiotensin II have on the renal arterioles?
Vasoconstriction of afferent AND efferent arterioles.
What do prostaglandins help prevent occurring in the kidneys?
Severe & potentially harmful vasoconstriction, renal ischaemia.
What effect do prostaglandins have on the renal arterioles?
Dampens the vasoconstrictive effects of sympathetic nerves of angiotensin II, especially on the AFFerent arterioles.
What stimulates the release of natriuretic peptides?
ANP & BNP released in response to increased pressure & circulating volume.
What is the myogenic response, and which arteriole does it affect?
Constriction in response to pressure - prevents vessel from being stretched, increases vascular resistance, and therefore prevents excessive increases in renal blood flow & GFR with BP rises. Affects the AFFerent arteriole.
What is tubule-glomerular feedback, and what effect does it have?
Increased arterial pressure increases GFR, which results in more Na+ & Cl- in the proximal tubule - this is sensed by the macula densa cells. These release paracrine agents to the AFFerent arteriole, triggering contraction and increasing vascular resistance - counteracts initial GFR increase.
What is the range of pH in body tissues?
7.35 to 7.45
What two processes generate acid & alkali in the body?
Diet & metabolism
What is an acid?
H+ donor
What is a base?
H+ acceptor
What is a weak acid?
HA <-> H+ & A- = partial dissociation
What is a weak base?
B & H+ <-> BH+ = partial dissociation
What time frame of adjustment to pH changes do kidneys need vs lungs?
Kidneys - days (metabolic) - lungs - rapid (respiratory)
What is the definition of a buffered solution?
Addition of an acid or base does not affect the pH of the solution
How do weak acids buffer?
The conjugate base (A-) of the partially dissociated weak acid (HA) neutralises the added acid
How do weak bases buffer?
The hydrogen ion (H+) from the partially dissociated weak base (BH+) neutralises added alkali
Name some physiological buffers (4)
Bicarbonate (HCO3-), phosphate (H2PO4-) & (HPO4^2-), plasma proteins, haemoglobin
What is the bicarbonate buffer system?
CO2 + H2O <-> H2CO3 <-> H+ + HCO3-
Which step of the bicarbonate buffer system is the slow step?
CO2 + H2O <-> H2CO3. Catalysed by carbonic anhydrase.
Which step of the bicarbonate buffer system is the quick step?
H2CO3 <-> H+ + HCO3-. Fast ionisation reaction.
What effect does increased CO2 in the blood have on pH?
pH decreases - acidosis!
Definition of acidemia?
An arterial pH below the normal range
Definition of alkalemia?
An arterial pH above the normal range
Definition of acidosis?
A process that tends to lower the pH of extracellular fluid
Definition of alkalosis?
A process that tends to raise the pH of extracellular fluid
What is NEAP?
Net Endogenous Acid Production (50-100mmol/day) - necessitates reclamation of filtered bicarbonate, and generation of new bicarbonate to neutralise the daily acid load.
What is secreted for every bicarbonate ion reabsorbed or generated in the tubules?
A H+ ion.
What would happen to urinary HCO3- excretion if a carbonic anhydrase-inhibiting drugs is administered?
Missing catalyst slows the slow step of the bicarbonate buffer. The bicarbonate is not reabsorbed. More HCO3- excreted in the urine. results in metabolic acidosis.
What does focal refer to in glomeruli?
Only some glomeruli affected
What does segmental refer to in glomeruli?
Part of the glomerulus is affected
What does diffuse refer to in glomeruli?
All glomeruli affected
What does global refer to in glomeruli?
The whole glomerulus is affected
What does cell proliferation mean?
Increase in the number of cells
What does cell expansion mean?
Increase in intercellular matrix
What does crescent refer to in glomeruli?
Proliferation of cells within Bowman’s space
What is the cause of intrinsic glomerulonephritis?
Antibody to the intrinsic glomerular antigens. e.g. Goodpastures, T4 collagen antibodies.
What is the cause of painted glomerulonephritis?
Antibody binds to ‘planted’ glomerular antigens. e.g. post-strep glomerulonephritis.
What is the cause of circulating complex glomerulonephritis?
Deposition of circulating antigen-antibody complexes. e.g. lupus nephritis
What is non-specific glomerulonephritis?
Non-specific deposition of circulating antibody. e.g. IgA nephropathy
Indications for renal biopsy? (5)
Nephrotic syndrome (adults), renal dysfunction of unknown cause (esp. acute), to guide treatment/assess prognosis when diagnosis is known, dysfunctional transplant kidney, sometime haematuria or proteinuria.
Contraindications to renal biopsy? (6)
Abnormal clotting/thrombocytopenia, drugs (aspirin, clopidogrel, warfarin, DOACs), uncontrolled hypertension (e.g. >170/100), single kidney, hydronephrosis, UTI
What 3 analyses are performed on renal biopsies?
Light microscopy (basic morphology/cellular infiltrate, special stains e.g. silver for collagen), Immunostaining (immunoglobulin or complement components), electron microscopy (ultrastructural detail,, including immune deposits)
Definition of nephrotic syndrome? (3)
Proteinuria (>3.5g/day), hypoalbuminaemia, oedema (& hyperlipidaemia, hypercoagilability)
Definition of nephritic syndrome? (5)
Haematuria, mild/moderate proteinuria, hypertension, oliguria, red cell casts in urine
What is the most common cause of nephrotic syndrome in children?
Minimal change disease
Treatment for minimal change disease?
Steroids (may relapse, may require heavier immunosuppression)
Causes of minimal change disease? (3)
Idiopathic, drugs (e.g. NSAIDs), lymphoma.
Presentation of Focal Segmental Glomerulosclerosis (FSGS)?
Nephrotic syndrome +/- renal impairment
Treatment for FSGS?
Steroids, immunosuppression - much less responsive than minimal change disease
Causes of FSGS? (5)
Primary. Secondary - obesity, IV heroin use, HIV, drugs (e.g. pamindronate)
Biopsy appearance of FSGS? (3)
Focal involvement, segmental sclerotic lesion, C3 & IgM deposition
What is the most common cause of nephrotic syndrome in adults?
Membranous nephropathy
Biopsy appearance of membranous nephropathy? (2)
‘Spikes’ on basement membranes, IgG deposition
Associated with membranous nephropathy? (3)
Malignancy, drugs (e.g. gold, penicillamine, captopril), infections (e.g. hepatitis, malaria)
What is the prognosis for membranous nephropathy? (3)
Rule of 3rds. 1/3 improve spontaneously, 1/3 stay the same, 1/3 develop progressive disease
Treatment for membranous nephropathy?
Immunosuppression - may respond.
Presentation of mesangiocapillary glomerulonephritis?
Nephritic or nephrotic syndrome
Biopsy of MCGN? (3)
Mesangial proliferation, thickened capillary walls (double contouring of basement membranes), positive immunofluorescence (e.g. C3)
Associated with MCGN? (3)
Infections (e.g. hepatitis, malaria, endocarditis, shunt nephritis), cryoglobulinaemia, malignancy
Can MCGN recur after kidney transplantation?
Yes
What commonly shows on histology in diabetic nephropathy?
Kimmelstiel-Wilson lesions - modular glomerulosclerosis
Clinical features of diabetic nephropathy? (3)
Initial low level proteinuria (microalbuminuria), heavier proteinuria (may be nephrotic), progressive decline in GFR
What is AL amyloidosis?
Light chain deposition, e.g. myeloma
What is AA amyloidosis?
Chronic inflammation, e.g. infection, CTD
What stain is used in amyloidosis?
Congo red - apple green birefringence under polarised light, with visible fibrils on microscopy.
How can renal amyloidosis present? (3)
Heavy proteinuria +/- nephrotic syndrome, +/- renal failure
What is Berger’s disease?
IgA nephropathy
What is the most common form of glomerulonephritis?
IgA nephropathy
Presentations of IgA nephropathy? (3)
Asymptomatic microscopic haematuria, episodic macroscopic haematuria (e.g. exercise, respiratory tract infection), progressive renal impairment/end stage renal failure. Presentations sooner that post-strep GN (after 2-3 days)
Associations with IgA nephropathy? (2)
Liver disease, Henoch-Schönlein purpura
Pathophysiology of IgA nephropathy?
Deposition of circulating IgA within the mesangium - leads to expansion of mesangial matrix, mesangial cell proliferation.
Presentation of post-strep GN?
2-3 weeks after a Group A strep infection (e.g. throat, skin), usually nephritic.
Biopsy findings post-strep GN? (4)
Neutrophil infiltration, mesangial & epithelial cell proliferation, IgG & C3 deposition, sub epithelial deposits
Treatment for post-strep GN?
Supportive care
Name two systemic vasculitides that can cause pouch-immune glomerulonephritis?
Wegener’s granulomatosis/granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA)
Biopsy findings renal vasculitis? (2)
Focal necrotising glomerulonephritis, crescents on biopsy
Treatment for vasculitic glomerulonephritis? (2)
Immunosuppression +/- plasma exchange
What antibodies cause Goodpasture’s/anti-GBM?
Antibodies to type 4 collagen
Presentation of Goodpasture’s? (2)
AKI, pulmonary haemorrhage. Rapid course.
Biopsy findings Goodpasture’s? (2)
Focal necrotising glomerulonephritis, crescents on biopsy but linear antibody deposition
Treatment for Goodpasture’s? (2)
Immunosuppression, plasma exchange
Presentation of rapidly progressive glomerulonephritis/crescentic nephritis? (2)
Nephritic syndrome, rapidly deteriorating renal function
Biopsy findings RPGN? (2)
Acute inflammatory process with crescent formation, cellular proliferation in Bowman’s space.
How many classifications of lupus nephritis are there, and what are they?
6 - normal glomeruli inc. minimal change, mesangial disease, focal proliferation, diffuse proliferation, membranous nephropathy, advanced sclerosis
Urine investigations? (4)
Dipstick (blood, protein, nitrites, leukocytes, nitrites, pH), microscopy (cells, casts, crystals), culture, protein quantification (24h collection)
Bloods for renal investigation? (4)
Haematology (FBC, ESR, coag, blood film), biochemistry (U&Es, LFTs, Ca, PO4, CRP), immunology (autoantibodies e.g. ANA, ANCA, anti-GBM, etc. Serum immunoglobulins & electrophoresis, Serum free light chains, Cryoglobulins, Complement levels), microbiology (blood cultures, serology e.g. hepatitis B/C, HIV, ASO titre/strep)
Imaging for renal investigation? (6)
CXR, renal USS, CT, MRI, angiography, nuclear medicine
Proteins in urine? (3)
Albumin, LMW proteins (beta-2 microglobulin, polypeptides, RBP), secreted proteins
What are the abnormal thresholds for ACR & PCR respectively?
ACR >3, PCR >15
What are the nephrotic range ACR & PCR values?
ACR >250, PCR >300
Types of benign proteinuria? (2)
Orthostatic proteinuria (children & adolescents, <3.5g/day), transient proteinuria - secondary to fever, heavy exercise, vasopressor, IV albumin (<1g/day)
Primary glomerulonephritides? (5)
Minimal change disease, Primary FSGS, Idiopathic membranous nephropathy, IgA nephropathy, Idiopathic membranoproliferative glomerulonephritis/MPGN
Secondary glomerulonephritides (6)
Diabetes mellitus, systemic amyloidosis, Secondary FSGS (e.g. obesity, HPTN, HIV), Autoimmune disease (e.g. SLE), Secondary membranous nephropathy (e.g. cancer, drugs), MPGN (hepatitis B/C)
Where in the nephron are LMW proteins processed? (2)
Filtered at the glomerulus, reabsorbed in the proximal tubule
What is overflow proteinuria?
Excess production of LMW proteins, exceeds reabsorptive capacity of tubules
What can cause overflow proteinuria? (3)
Myeloma (free light chains), rhabdomyolysis (myoglobin), haemolysis (haemoglobin)
What can cause post-renal proteinuria? (2)
Inflammation or lower urinary tract - infection, stones.
What two things is proteinuria a known risk factor for?
Cardiovascular disease, progressive CKD
Why does nephrotic syndrome include thrombosis risk?
Decreased concentrations of antithrombin III & plasminogen
General management for nephrotic syndrome? (5)
Low sodium diet & fluid restriction, diuretics, RAAS inhibition & blood pressure control, statin, anticoagulation
Nephrotoxic drugs? (13)
ACEI, ARB, diuretics, methotrexate, statin, gentamicin, vancomycin, bisphosphonates, calcineurin inhibitors (e.g. ciclosporin, tacrolimus), lithium, mesalazine, NSAIDs, CT contrast
At what week does the ‘permanent’ kidney form, and what is it called?
Week 5, metanephros
What is renal genesis?
One or both kidneys fail to develop
What is pelvic kidney?
A kidney fails to ascend, is stuck in pelvis. Can function normally. Ureter could cause strangulation.
What is horseshoe kidney?
The kidneys are fused together at the lower end or bases.
What is the function of ACE/angiotensin converting enzyme?
Converts angiotensin I to angiotensin II
Where does renin act?
Conversion of angiotensinogen to angiotensin I.
What increases release of renin? (4)
Low arterial BP, low BP in glomerular blood vessels, increased loss of Na+/water, increased sympathetic activity
What decreases release of renin? (3)
Na+/water retention, increased BP, activation of AT1 (angiotensin II type I) receptors (short loop negative feedback
What 3 things control renin secretion?
Macula densa pathway, intrarenal baroreceptor pathway, beta-receptor pathway
Where is renin stored & secreted from?
Juxtaglomerular cells in granules.
How does the intrarenal baroreceptor pathway affect renin release?
Detected increase in BP or renal perfusion pressure in preglomerular vessels - inhibits renin release.
What type of feedback loop are renin and angiotensin II in?
Short loop negative feedback. Increased renin causes increased angiotensin II.
What pharmacological agents decrease renin release? (3)
NSAIDs (inhibit PG synthesis), centrally acting sympatholytic agents & beta blockers (reduce beta-receptor activation), ACEI/ARB/renin inhibitors
How do loop diuretics affect renin release?
Decrease BP, and increase NaCl reabsorption - causes increased renin release.
What enzymes act as an alternative pathway for angiotensinogen -> AngI or directly AngII? (5)
Cathepsin, tonin, cathepsin G, chymostatin-sensitive angII generating enzyme, heart chymase
What does angiotensin II rapid pressor response do? (2)
Constricts AFFerent arterioles, weak vasoconstriction in splanchnic vessels, brain, lungs, and skeletal muscle.
What does angiotensin II slow pressor response do? (5)
Reduces urinary excretion of Na+/water, increases excretion of K+, stimulates Na+/H+ exchange in the proximal tubule (increases Na+, Cl- & bicarb reabsorption), increases Na+ glucose symporter in proximal tubule expression, directly stimulates Na+/K+/2Cl- symporter in the thick ascending limb
Effects of aldosterone antagonists? (3)
Na+/water loss, hyperkalaemia, acidosis risk
What is classed as mild hyponatremia?
130-135mmol/L
What is classed as moderate hyponatremia?
125-129mmol/L
What is classed as profound hyponatremia?
<125mmol/L
Presentation of acute hyponatremia? (3)
Seizures, coma, respiratory distress - severe cerebral oedema
Presentation of chronic hyponatremia? (7)
Frequently mild/asymptomatic, headache, restlessness, muscle cramps, nausea & vomiting, lethargy, confusion & disorientation - adaptation minimises cerebral oedema, risk of injury from over-treated hyponatremia!
What condition does overly rapid hyponatremia correction put the patient at risk of?
Central pontine myelinosis/osmotic demyelination syndrome
What is TURP syndrome?
Trans-urethral resection of prostate - too much hypotonic irrigation fluid is absorbed into the bloodstream during the operation, results in volume overload.
Management of TURP syndrome? (4)
Supportive care of cardiac & respiratory functions (including airway protection if necessary), fluid restriction, furosemide, hypertonic saline.
What is SIADH?
Syndrome of Inappropriate Antidiuretic Hormone Secretion - results in hyponatremia with hypervolaemia or euvolaemia
What is ADH also known as?
Vasopressin
What causes SIADH? (9)
Central nervous system disorders (trauma, psychosis, stroke, infection, haemorrhage), malignancy (especially small cell lung cancer), drugs (e.g. carbamazepine, SSRIs, cyclophosphamide), surgery (pain afferents?), pulmonary disease (pneumonia, atelectasis, asthma, pneumothorax), hypopituitarism/hypothyroidism, vasopressin/desmopressin/oxytocin, HIV, hereditary
What drugs commonly cause hyponatremia? (8)
Thiazides, amiloride, carbamazepine, sulphonylureas (NOT gliclazide), PPIs, SSRIs & antidepressants, ACEI & ARBs, opiates
What is beer potomania?
Patient with low daily solute intake & excessive beer consumption (which is low in sodium) - euvolaemic hypotonic hyponatremia
Diagnostic criteria for SIADH? (6)
Effective serum osmolality <275mOsm/kg, urine osmolality >100mOsm/kg, clinical euvolaemia, urine Na+ >30mmol/L with normal dietary salt & water intake, absence of adrenal/thyroid/pituitary/renal insufficiency, no recent diuretic use.
Hyponatremia assessment? (8)
Water gain & water loss, confirm not pseudohyponatremia, identify any heart/liver/kidney failure, check if on thiazide diuretics, assess volume status, compare urine & serum osmolality, urinary sodium, TFTs/AM cortisol/ACTH stimulation
What is pseudohyponatremia?
Spuriously low serum Na+ with normal serum osmolality. Check for additional solute that may affect lab result.
What are the 5 Rs of adult IV fluid therapy?
Resuscitation, Redistribution, Routine maintenance, Replacement, Reassessment
What are some examples of redistribution in consideration for IV fluids? (4)
Oedema, hypoalbuminaemia/low oncotic pressure, sepsis, acute pancreatitis (third-spacing)
Clinical signs of shock? (8)
Low systolic blood pressure (<100mmhg), BPM >90, RR <20, delayed capillary refill time (>2s), cool peripheries, high/deteriorating EWS (early warning score), response to passive leg raise/PLR, confusion/decreased/loss of consciousness
What is a bolus of IV fluids in a normal pt? ml & mins?
500ml - 15 mins
At what ml given should you seek expert assistance when you have been delivering IV fluids?
2000 - 2L or more.
What is a colloid fluid?
A fluid with lots of starch/protein components
How many ml/kg body weight/day do normal people need of water?
25-30ml/kgbw/day
How many mmol/kgbw/day of sodium, potassium, and chloride do normal people need?
1-2mmol/kgbw/day
How many g of glucose per day does a normal person need?
50-100g/day
Normal 0.9% saline - how many mmol or g Na+, K+, Cl-, HCO3-, Glu?
Na+ 154, K+ 0, Cl- 154, HCO3- 0, Glu 0g
5% dextrose - how many mmol or g Na+, K+, Cl-, HCO3-, Glu?
Na+ 0, K+ 0, Cl- 0, HCO3- 0, Glu 50g
Hartmann’s solution - how many mmol or g Na+, K+, Cl-, HCO3-, Ca2+, Glu?
Na+ 131, K+ 5, Cl- 111, HCO3- 29, Ca2+ 2 Glu 0g
What should be taken into account when calculating fluids? (3)
How much is being lost - urination, vomiting, diarrhoea, stoma output, NG tube output. How much is going in - oral intake of liquid & food, medications, IV administration, surgery. Inappropriate fluid loss - third-spacing, bleeding, oedema, etc.
What can excessive vomiting cause?
Hypochloraemic/hypokalaemic metabolic alkalosis.
How do you correct hpochloraemic/hypokalaemic metabolic alkalosis?
Supplemental K+ & Cl-
What two ions are predominantly lost in ileum via stoma or fistula?
Na+, Cl-
Where is the primary distribution for 5% glucose solution IV?
Intracellular
Where is the primary distribution for colloids IV?
Plasma volume
Where is the primary distribution for 0.9% normal saline?
Interstitial & lymphatics, also plasma volume.
pH of normal saline 0.9%?
4.5-7
pH of 5% glucose/dextrose?
3.5-5.5
pH Hartmann’s?
5-7
When would you consider using Human Albumin Solution (HAS) 4.5%/20% for fluid resuscitation? (4)
Severe sepsis, therapeutic plasma exchange, large-volume paracentesis (3L), hepato-renal syndrome
Treatment for hypovolaemic hyponatremia?
Continuous normal saline, regular U&Es monitoring
Treatment for euvolaemic hyponatremia?
Consider SIADH - fluid restriction, usually <1L/day. Paired urine & serum osmolality.
Treatment for hypervolaemic hyponatremia? (3)
HoWater restriction, consider diuretics if overload symptomatic - <6mmol/day correction, SLOW.
How to manage fluid resus in CKD/dialysis patients? (2)
SMALL boluses with reassessment of fluid responsiveness every time. Potassium/phosphate restricted (even calcium, sodium) - consider this.
What form of calcium is not excreted by the kidneys?
Protein-bound
Total serum calcium
Ionised (active) calcium + protein-bound calcium
What does adjusted calcium give a better idea of?
Ionised calcium levels
What should also be considered alongside calcium level?
Serum albumin
What is released when low serum calcium is detected by parathyroid gland receptors?
PTH is released
What effect does PTH have? (5)
Acts on distal convoluted tubule = more calcium reabsorption, increases osteoclastic activity, more intestinal calcium absorption, increased bit D hydroxylation/activation, more phosphate excretion
Vitamin D relevance to calcium levels?
Activates osteoblasts, which stimulate osteoclasts - calcium release
What effect does calcitonin have?
Opposite of PTH - reduces PTH, decreases vitamin D activation on detection of hypercalcaemia.
What supplement do you give to CKD patients with vitamin D deficiency?
Calcitriol
Why do you give calcitriol in CKD for vit D deficiency?
Activated vitamin D - bypasses the activation step in the kidneys.
Causes of hypocalcaemia? (3)
Hypoventilation, alkalosis (bind more ionised Ca2+!), decreased intake (GI, bones, excess loss, inadequate intake)
Causes of hypercalcaemia? (3)
Excess intake, excess loss from bones, increased mobilisation from bones
Calcium has what effect on muscle contraction?
More calcium delays depolarisation (slowing action potential, less muscle contraction), less increases depolarisation (more muscle contraction)
