ESA 3 Clinical Conditions Flashcards
Renal agenesis
A lack of development of kidney (or part of the kidney), usually due to failure of the ureteric bud to interact with the metanephric blastema and stimulate the future metanephros to grow. Requires bilateral to show symptoms (can survive with 50% renal function)
Wilm’s tumour
A congenital malignant tumour of the metanephric blastema. Usually occurs in otherwise well children. Responds very well to treatment (>90% 5 year survival)
Duplication defect
The ureteric bud splits before it stimulates metanephros, which results in either an extra entire kidney forming or (more commonly) the kidney being divided into two lobes which together equal an entire kidney’s renal function. Usually leads to the extra kidney/lobe giving rise to an ectopic ureteric orifice (see below)
Horseshoe kidney
The fusion of the kidneys in the midline by their inferior poles during ascent. This leads to them lying just inferior to the inferior mesenteric artery as the isthmus (fused bit in middle) snags on the IMA as it emerges from the abdominal aorta. Usually asymptomatic
Ectopic ureteric orifice
The ureter opens into somewhere other than the trigone of the bladder e.g. rectum or vagina. Causes incontinence and can cause chronic inflammation due to the epithelia of the new opening not being specialised to deal with urea content
Cystic kidney disease
Can be either multicystic (leading to atresia of ureter) or polycystic (autosomal recessive, incompatible with life, only live about a week). Detected by presence of oligohydramnios during foetal
development
Urorectal fistula
Usually due to a defect in the urogenital sinus leading to a failure of cloacal portioning. Leads to communication between urinary and GI tracts. Leads to infection due to colonic flora and irritation due
to urea content
Exstrophy of the bladder
A result of incomplete obliteration of the allantois/urachus leading to bladder opening onto the abdominal wall and leakage of the urine through the umbilicus (so incontinence)
Ectopic urethral orifice
The urethra opens into somewhere other than the correct place on the external genitalia (e.g. vagina or rectum). Leading to incontinence
Hypospadia
A defect in union of urethral folds in males. Leads to the urethra opening onto the ventral surface of the penis (underside) rather than the end of the glans. Could be related to having older parents
Hypertension (due to renovascular disease)
Renal artery stenosis or aneurysm leads to a reduced perfusion pressure in the kidney. This is detected by the cells of the macula densa and as a result of increased renin release more AT2 is created.
Its effects are:
o Peripheral vasoconstriction through breakdown of bradykinin
o Inc. aldosterone release which leads to inc Na+ reabsorption (DCT/collecting duct) and subsequent
o Stimulates Na+ reabsorption at DCT directly
Diabetes insipidus
Creation of large amounts of dilute urine due to either a lack of production of ADH (neurogenic) or insensitivity of ADH (nephrogenic). Leads to dangerous dehydration, can be treated by ADH injections/nasal spray
Syndrome of inappropriate ADH production (SIADH)
Huge overactivity of ADH production (usually pituitary adenoma) which leads to excessive fluid retention and dilutional hyponatraemia (fluid vol Inc. to the point that Na+ osmolarity drops). Need to remove the source of the hyponatraemia, which can lead to systemic cell lysis and death
Hypercalcaemia definition
[Ca2+] >2.5mmol/L
Hypercalcaemia Causes (common)
Haematological malignancies (such as Hodgkin’s lymphoma)
Non-haematological malignancies (such as osteosarcoma)
Primary hyperparathyroidism (Inc. PTH)
Vit D toxicity
Hypercalcaemia Symptoms
Stones – Inc. likelihood of renal calculi formation due to supersaturation of urine with Ca2+
Moans – cognitive impairment depression (also leads to drowsiness, apathy, coma etc)
Groans – anorexia, nausea/vomiting, constipation (due to impairment of peristalsis)
Bones – bone pain due to breakdown to obtain Ca2+ (common in primary hyperparathyroidism)
Thrones – polyuria due to Inc. Ca2+ in tubular lumen
Also causes hypertension and shortened QT interval on ECG
Hypercalcaemia Treatment
Hydration (force Ca2+ diuresis)
Furosemide (loop diuretic)
Not thiazides as they spare Ca2+
Bisphosphonates (protect bone from breakdown)
IV calcitonin (debatable, does it really do anything in anyone that’s not pregnant?)
TREAT UNDERLYING CONDITION
Renal calculi definition
A stone within the collecting system of the urinary tract
Types and common locations of renal calculi
Calcium – 80% (radio-opaque)
Urine becomes saturated with calcium and oxalic acid (dietary; chocolate, nuts,
Struvite – 5% (big stones)
Urate – 5% (radiolucent)
Other types less common and not worth learning unless you’re a consultant urologist…
Ureteropelvic junction (as the ureter begin at the renal pelvis)
Ureteric crossing of the iliac vessels/pelvic brim
Ureterovesical junction (when they end at the bladder)
Renal calculi symptoms
Haematuria
Renal colic – rolling around on the floor w/ flank pain – worst thing patient has ever felt (even > childbirth)
Persistent dull ache w/ exacerbations
Manifestations of post-renal AKI (see below) if it obstructs both kidneys (e.g. bladder neck) or patient only has one kidney
Symptoms of pyelonephritis if infection sets in due to stasis
Nausea
Inc. need to urinate/urinary urgency
Renal calculi Investigations
Bloods to check PO43-, PTH and Ca2+ levels
Abdominal X ray (AXR) to spot radio-opaque stones (Ca2+ oxalate)
USS
Non-contrast CT (after neg AXR)
Renal calculi Management
Small stones (6mm) – several options
Extracorporeal shockwave lithotripsy (ESWL) – use vibration to obliterate stone, non
Ureteroscopy (in through urethra)
Open surgery (very rare)
Hyperkalaemia definition
[K+] >5mmol/L
Causes of hyperkalaemia
External balance dysfunction
Increased intake (either inappropriate IV or dietary, but dietary only a problem with CKD) Decreased excretion (AKI/CKD, combination of ACE inhibitors (ACEi) and K+ sparing diuretics (amiloride), low aldosterone e.g.. Addison’s disease etc.)
Internal balance dysfunciton
DKA – no insulin (promotes ECFICF of K+), plasma hyperosmolarity (K+ leaves cell) and metabolic acidosis (H+ uptake K+ leaves cell)
Cell lysis – tumour lysis syndrome, crush injury
Metabolic acidosis – e.g. Inc. [lactate]
Hyperkalaemia Symptoms
Heart Predictable ECG changes (LIFE THREATENING) Tented T waves Prolonged PR interval, ST depression QRS widening VF Asystole
GI Paralytic ileus (depolarises membrane and leaves Na+ channels inactive inability of muscular contraction) Acidosis – K+ uptake into cells promotes movement of H+ to ECF
Hyperkalaemia Acute management
IV calcium gluconate – protect the heart
Shift K+ into ECF – insulin and dextrose, salbutamol
Remove K+ (dialysis) – last resort
Hyperkalaemia Long term management
Change diuretics, treat DKA etc.
Reduce dietary intake
Gut resins to bind K+ to inhibit dietary uptake
Hypokalaemia definition
[K+]
Hypokalaemia causes
External balance dysfunction – excessive loss via GI (D and V, bulimia etc.) or renal (loop diuretics, diabetes mellitus or insipidus, high aldosterone e.g. Cushing’s)
Internal balance dysfunction – metabolic alkalosis (following vomiting, alkaline tide)
Hypokalaemia Symptoms
Heart – predictable ECG change
Hyperexcitability due to hyperpolarisation
Low/absent T waves (no pot, no tea!)
GI
Paralytic ileus (hyperpolarizes membrane leads to (hyperexcitability
leading to inability of muscular contraction)
Skeletal muscle – same principle as paralytic ileus leading to muscle weakness
Renal – unresponsive to ADH leading to nephrogenic diabetes insipidus
Acute management of hypokalaemia
Treat cause (Cushing’s, diuretics etc.)
Replace K+ (dietary/IV – BE CAREFUL WITH IV)
Consider spironolactone/ACEi with excessive mineralocorticoid activity
UTI definition
Colonization of the urinary tract with bacteria (normally sterile)
UTI Types
Simple/uncomplicated (lower aka cystitis) – woman of reproductive age, most common
Complicated (lower aka cystitis) – men, children of both genders, uncommon
Pyelonephritis (upper) – inflammation of renal pelvis, can cause AKI/CKD
Can lead to septicaemia/septic shock
Chronic nephritis
UTI Influencing factors
Host
Gender (female urethra shorter, shorter distance from perianal area to bladder)
Obstruction of collecting system (benign prostatic hyperplasia, tumour, pregnancy,
Neurological lesion leading to incomplete emptying therefore stasis and infection
Ureteric reflux (angle of ureterovesical junction changes as we enter puberty) leading to ascending bladder infeciton in children
Comorbidities – diabetes, CKD, AKI, hypertension, endocarditis etc.
Bacteria
Fimbrae – epithelial attachment
Haemolysins leading to damaged host membranes leading to nutrition
K antigen on polysaccharide capsule leading to evasion of macrophages
Urease leading to NH3 production for bacterial growth
Bacteria that fits most of this is E coli
Can also be other enterobacteriacae, enterococci (atypical pathogen, rings alarm bells) or staphylococci
Symptoms of cystitis
Frequent urination
Pyuria (burning/stinging when peeing)
Bad smelling urine
Cloudy urine
Malaise
Symptoms of pyelonephritis
Fever and chills (shivering)
Nausea and vomiting
Renal pain
SIRS if severe
Investigations of UTI
Urine sample
Cloudiness – if it’s cloudy it’s almost always bacteria
Nitrite/leukocyte esterase dipstick – bacterial metabolic byproduct and immune response indicate bacteria
MCS of urine sample (complicated/pyelonephritis/comorbidities e.g. endocarditis, CKD)
WBC/RBC count
Culture for pathogens
Treatment of UTI
Conservative – Inc. fluid intake, address comorbidities/underlying conditions
Antibiotics
Uncomplicated – 3 days trimethoprim (consult trust policy wherever you are)
Complicated – 7 days trimethoprim/nitrofurantoin
Pyelonephritis – 14 days ciprofloxacin/cefuroxime
Can give low dose trimethoprim/nitrofurantoin as prophylaxis for recurrent UTI
Chronic nitrofurantoin exposure leading to interstitial lung disease in some people
Stress urinary incontinence (SUI) definition
Stress urinary incontinence (SUI) – urinary incontinence (involuntary passing of urine) in response to exertion (coughing, sneezing etc.). Precipitated by exertion
History of SUI
Childbirth
Previous pelvic surgery
Examination of SUI and UUI
Weight/height (obesity lead to Inc. risk of both types of urgency)
Abdo exam (exclude palpable bladder for overflow incontinence)
Female – external genitalia stress test (get them to cough)
Male – prostate exam (hyperplasia)
Investigation of UUI and SUI
Urine dipstick (nitrites indicate UTI, haematuria indicate malignancy, proteinuria, glucose indicates osmotic diuresis and overflow incontinence)
Frequency and volume chart (urine in and out)
Bladder diary (can help to work out SUI vs UUI)
Pressure/flow studies (invasive)
Treatment for SUI
General
Decrease fluid/caffeine intake
Avoid constipation
Stop smoking
Contained incontinence
Indwelling catheter (risk of infection)
‘condom catheter’ – sheath device
Incontinence pads
Conservative
pelvic floor exercises (3x 8 reps a day, every day for 3 months minimum)
Pharmacological dulotexine (NorAd/serotonin uptake inhibitor which increases activity of the external urethral sphincter in the filling phase leading to continence)
Surgical
Female
Low tension vaginal tapes – support mid urethra
Retropubic suspension procedure – correct position of bladder neck leading to continence
Classical fascial sling – use tensor fascia lata/rectus sheath to support urethra and bladder outflow leading to continence
Intramural bulking agents – inject substance (fat, collagen etc.) into urethral walls to decrease lumen size leading to increase continence (Temporary measure)
Male – artificial urethral sphincter – hydraulic device with control in the scrotum leadign to artificial continence the patient can turn on and off when urinating required
Urge urinary incontinence (UUI) definition
Urinary incontinence preceded/accompanied by urgency
UUI History
Preceding urgency
UUI Treatment
General
Decrease fluid/caffeine intake
Avoid constipation
Stop smoking
Contained incontinence
Indwelling catheter (risk of infection)
‘condom catheter’ – sheath device
Incontinence pads
Conservative – voiding scale training
Void every hour, hold or let it leak in-between
Increase duration between voiding by 15 to 30 minutes per week until 2 or 3 hours
Pharmacological
Cholinergic antagonists (oxybutynin, could theoretically use atropine) Block M3 receptors detrusor relaxation less urge to void Nasty side effects from stimulation of other muscarinic ACh receptors e.g. dry eyes, dry mouth, constipation, tachycardia etc. – think exaggerated fight or flight response
B3 adrenoceptor agonist (mirabegron)
Stimulates B3 adrenoceptors detrusor relaxation less urge to void
Not many off target side effects
Botulinum toxin (Botox) Injected into detrusor and blocks ACh release at M3 receptors leading to loss of detrusor contraction – last resort as semi permanent (min 6 months)
Surgical – last resort
Sacral nerve neuromodulation
Augmentation cystoplasty (bowel used as bladder)
Urinary diversion (e.g. send it to GI tract instead)
Acute Kidney Injury (AKI) definition
AKI itself can be defined as the same general thing irrespective of the cause:
Clinical syndrome encompassing abrupt decline in GFR, increased [NH3] and [urea], acid/base disturbance and Na+ upset
AKI is categorized into stages of severity:
- Serum creatinine (SCr) >26.5mmol/L or >150% patient’s baseline
- SCr >200% baseline
- SCr >354mmol/L (w/acute rise of >44mmol/L in 300% baseline
Pre-renal acute kidney injury definition
Renal insult due to hypoperfusion of the kidney
Pre-renal acute kidney injury causes
Causes – anything that causes decreased O2 delivery to >50% of kidney parenchyma (so has to be bilateral/patient only has one kidney)
Hypovolaemia
Systemic vasodilation e.g. septic/anaphylactic shock
Left ventricular failure (STEMI, severe valvular disease, cardiac tamponade leading to mechanical shock, tension pneumothorax etc.)
Renal artery aneurysm/stenosis/thrombus/embolus
Can also have impairment of renal auto regulation
Preglomerular vasoconstriction caused by sepsis, NSAID overdose, hypercalcaemia etc.
Postglomerular vasodilation caused by ACE inhibitor/AT2 antagonist overdose
Pre-renal acute kidney injury Pathophysiology
Decreased Na+ delivery to macula densa (a result of decreased GFR) causes paracrine prostaglandin release to dilate afferent arteriole
In a small GFR change, this is usually enough to correct the defect e.g. minute to
Decreased Na+ delivery to macula densa (a result of decreased GFR) causes renin release which eventually leads to angiotensin II release
This causes efferent arteriole vasoconstriction, can also correct the defect, more
Due to the fact that it is trying to compensate, it is responsive to fluid resuscitation (circulating vol Inc. leading to preload Inc. leading to CO Inc. leading to renal perfusion Inc.)
Acute tubular necrosis definition
A result of decompensation following pre-renal AKI that sees the loss of function of the tubular cells
Cells of PCT very metabolically active so sensitive to loss of O2, without O2 can’t generate ATP to power Na+/K+ATPase to set up concentration gradient for isosmotic reabsorption
Instead, fluid just flows through and out into urine at a constant rate like a sand timer/sieve
This means that kidneys can no longer respond to changes in osomolarity so fluid resuscitation can lead to dilutional hyponatraemia
So you have to distinguish between pre-renal AKI and ATN to give correct treatment
Causes of Acute tubular necrosis
Ischaemia
Nephrotoxins – all drugs considered nephrotoxins until proven otherwise
Can also have endogenous nephrotoxins e.g. myoglobin, bilirubin
Rhabdomyolysis – huge breakdown of skeletal muscle (trauma) causes huge myoglobin release, which is a nephrotoxin leading to ATN
Intrinsic renal acute kidney injury
Any pathological process that actually affects the renal parenchyma
Glomerular disease – see nephritic syndromes below
Essentially, inflammation/immune response clogged glomerulus leading to decline in GFR
Primary – only affect glomeruli e.g. IgA nephropathy
Secondary – part of a wider immune response e.g. Lupus, vasculitis
Acute tubulo-interstitial glomerulonephritis – infection (usually) as a consequence of pyelonephritis
Can also be toxin induced (nephrotoxic drugs; penicillins, NSAIDs, omeprazole etc.)
Other causes – linked by common pathology of endothelial damage leading to microvascular thrombi leading to occlusion of small arteries microangiopathic haemolytic anaemia leading to dec O2 delivery to renal parenchyma
Haemolytic uraemic syndrome – preceded by a bout of infectious diarrhea
Malignant (severe) hypertension
Pre-eclampsia (hypertension during pregnancy)
Post-renal acute kidney injury
Obstruction of the collecting tract
Inc. intraluminal pressure leading to backup leading to hydronephrosis thus renal impairment
3 main types Intraluminal – RENAL CALCULI, thrombus, tumour etc. Within wall (usually causes CKD not AKI) – post TB stricture etc. Extrinsic – hyperplastic prostate, tumour, aneurysm (abdo aorta/uterine artery) etc.
Almost always causes renal colic and haematuria
The AKI patient common presentation (all types)
Tend to be elderly
Hypotensive (BP should be measured as a difference from the norm e.g. an elderly man with angina, hypertension, ACEis and diuretics at 120/80 is essentially hypotensive)
Nauseated, lethargic
Pre-renal AKI symptoms
Hypovolaemic shock – tachycardia, hypotensive, peripheral cyanosis, dec JVP
Septic shock – tachycardia, hypotensive, red and warm peripheries, dec cap refill time, rigors, pyrexia
Renal AKI symptoms
Nephrotoxic drug history
Urinary tract infection (see above)
Trauma (rhabdomyolysis, particularly in the elderly)
Post-renal AKI symptoms
RENAL COLIC – flank pain T11-L3, patient will roll around to try and stop it
Anuria
Palpable bladder
Potentially an enlarged prostate
Investigations of AKI
Urinalysis
Nitrites (UTI)
Blood and protein (nephritic syndrome leading to renal AKI)
Urine biochemistry – pre-renal vs ATN
Pre-renal leading to huge ATII release thus high urine osmolarity w/ low [Na+]
ATN leading to decompensation and loss of function and thus low urine osmolarity (similar to ECF osmolarity as no reabsorption has taken place) w/ high [Na+]
Serum biochemistry – shows immediate concerns/complications
In all cases, [urea] and [creatinine] are Inc.
Hypocalcaemia (and potentially hyperphosphataemia)
Hyponatraemia a result of fluid overload (dilutional) or acute tubular necrosis (pee it all out)
Hyperkalaemia – WILL KILL PT IF YOU’RE NOT CAREFUL
Imaging
USS – query obstruction/no change in pre-renal despite fluid resuscitation (check for stenosis/aneurysm)
CXR – assess fluid overload and/or infection (TB, peritonitis etc.)
AXR – look for radiopaque stones (USS probably better for this)
Renal biopsy – differentiates types of renal AKI when you’re not sure (glomerulonephritis, acute tubular necrosis and acute tubulo-interstitial nephritis show different histology because they’re different parts of the kidney)
Management of AKI
Pre-renal – correct the fluid balance (hypovolaemia) and underlying insult (sepsis leading to septic shock)
Surgery on renal arteries if needed
ATN – supportive of normal body homeostasis
Renal – supportive of normal body homeostasis (so carefully monitor fluid intake and treat ion imbalances/acidosis/alkalosis) and treat the specific cause (see below for some common causes of nephritic syndrome)
Post-renal – remove blockage
Dialysis is a last resort – only indicated in some cases
Persistent hyperkalaemia despite treatment (B2 agonists, calcium gluconate, binding resins, insulin and dextrose, discontinue K+ sparing diuretics e.g. amiloride)
Fluid overload despite treatment (diuretics, strongest ones are loop diuretics as this is where the most Na+ reabsorption occurs out of all diuretic targets)
Metabolic acidosis where supplementary NaHCO3 is contraindicated
Dialysable nephrotoxin e.g. antifreeze
Severe uraemia (pruritus, pericarditis, dec GCS, nausea and vomiting)
Nephrotic syndrome definition
Characterized by >3.5g protein lost through urination in
Focal segmental glomerulosclerosis
Presents in adults
Focal segmental glomerulosclerosis = scarring in isolated area of glomerulus that leads to
Can progress to renal failure, doesn’t respond well to steroids
Known to be caused by an immune factor (we just don’t know what this factor is) as filtration dysfunction (generic scar tissue which are not specialized for filtration making them leaky) transplanted kidneys also suffer
Minimal change glomerulonephritis
Presents in adolescents, worsening proteinuria
Minimal change = normal under LM but shows podocyte damage under TEM
Unknown pathogenesis but can respond to steroids and not likely to progress to renal failure
Membranous glomerulonephritis
Most common in adults
Immune deposits in the sub-epithelial space lead to thickened capillary loop lead to leaky membrane leading to proteinuria
Follows the rule of 1/3rds (1/3rd get better, 1/3rd show no change (no renal failure) and 1/3rd progress to renal failure)
Tends to be associated with lymphoma
Nephritic syndrome definition
Damage to the glomerulus leading to significant haematuria along w/ proteinuria (pores large enough to allow RBCs through) and decreased renal function as a result
IgA nephropathy
Most common cause of nephritic syndrome (and commonest type of glomerulonephritis)
Presents at age with visible or invisible haematuria
Known to have a relationship with mucosal inflammation as IgA protects mucosal surfaces
Histological findings are varied, by mesangial proliferation and scarring w/ a positive IgA stain are usually seen
Significant proportion leading to CKD and eventual renal failure
Thin GBM nephropathy
One of two common hereditary nephropathies, and the more benign.
Thin GBM leads to isolated haematuria, doesn’t really progress to any sort long term renal damage
Alport syndrome
X linked recessive abnormal collagen IV structure leading to dysfunction of the basement membrane
As collagen IV isn’t exclusive to the kidneys, deafness (ear BM dysfunction) also seen
Usually progresses to renal failure
Exists on a spectrum with thin GBM nephropathy
Goodpasture syndrome
Aka anti-GBM disease
Overnight onset of severe nephritic syndrome due antibody to collagen IV
Typically only affects GBM, and not ear (no one knows why)
Associated with pulmonary haemorrhage in smokers due to alveolar BM damage (not seen in people with healthy lungs)
Can be treated with complete immunosuppression and IgG plasmophoresis if caught early enough
Vasculitis
Systemic inflammation of blood vessels (kidney is well vascularized and therefore affected)
Blood vessels directly attacked by ANCA (anti-neutrophil cytoplasmic antibody) and neutrophils
Histologically appears as segmental necrosis, but can be treated if caught early enough
Prostate cancer
Risk factors Why don’t we screen? Presentation Investigation Treatment
Carcinoma of the prostate (usually)
Risk factors
Increased age
Ethnicity (black>white>Asian w/ Asian as lowest risk)
Family history – BRCA2 gene
Why don’t we screen?
Won’t improve QOL/life expectancy in a significant amount of patients
Prostate specific antigen isn’t specific to prostate cancer, just a general pathology of the prostate
Presentation – elderly, haematuria (advanced cases), renal colic – USUALLY ASYMPTOMATIC
Bone pain from mets (usually sacrum/hip)
Investigation – rectal exam, PSA blood test, bone scan (for mets) and transrectal ultrasound biopsy
Treatment – depends the severity of the disease
Localised – surveillance (especially elderly, not worth the hassle), radical prostatectomy or radiotherapy (external vs local radioactive beads in rectum)
Advanced localized – surveillance, hormones or radiotherapy
Metastasised – surgical/medical castration w/ LHRH agonists (overload receptors, shuts down the feedback loop and it stops functioning) which slows growth, bisphosphonates to protect bone and chemo/radiotherapy
Bladder cancer
Risk factors
Staging
Treatment
Usually a carcinoma
Risk factors – smoking, schistosomiasis (only really seen in developing world), occupational exposure to carcinogens (rubber/plastic/oil industry)
• Staging – based on TNM but T types are specific of course:
• T1 – up to submucosa
• T2 – penetrated 50% but
Renal cell carcinoma
Risk factors
Common Metastasise
Treatment
Risk factors – smoking, obesity, dialysis
Mets are common
Perinephric spread leading to secondary renal tumours
Lymphatic spread leading to nodal mets
Venous drainage leading to IVC obstruction w/ ‘tumour clot’
Treatment – surveillance, radical nephrectomy
Palliative – molecular angiogenesis antagonists e.g. sunitinib
Upper tract transitional cell carcinoma
Cancer from the kidney down to the trigone
Uncommon, but related to smoking, phenacetin (discontinued painkiller) use and Balkan’s nephropathy (type of familial interstitial nephritis)
Leads to hydronephrosis (tumour leading to obstruction)
Needs a radical removal of kidney, fat, ureter and part of trigone
Chronic kidney disease (CKD)
Defined as the irreversible and progressive degeneration in renal function over months to years. Universal pathological feature is replacement of renal parenchyma with fibrous scar tissue leading to shrunken, fibrotic kidney that’s no longer specialized for function
Classification of CKD
Classified into several stages (numbers aren’t that important):
GFR based - >90ml/min/1.73m2 is G1 (has to show some underlying pathology etc. polycystic kidney) whilst 30
These two scores combined to give a staging code e.g. G3aA3
Causes of CKD
DIABETES
HYPERTENSION
Renal artery sclerosis
Infection e.g. chronic pyelonephritis
Genetic e.g. Alport’s
Obstruction/reflux nephropathy e.g. renal calculi hydronephrosis
Idiopathic
Presentation of CKD
CKD has effects spanning several bodily systems
Cardiovascular -atherosclerotic plaque formation, hypertension and subsequent cardiac damage (ATII release) and uraemic pericarditis
Ca2+ regulation
Decrease in tubular function loss of Ca2+ in filtrate and increased retention of H3PO4-
Also, creation of active Vit D decreased (osteomalacia) [Less dietary absorption]
Hypocalcaemia causes PTH release and subsequent bone breakdown to generate free Ca2+ (known as osteititis fibrosa cystica)
Bone breakdown seen in vertebrae (rugby jersey spine) and terminal phalanges -known as renal osteodystrophy
Disarray in Ca2+ metabolism can lead to metastatic/dystrophic calcification (seen in aorta, synovial joints etc.)
Bodily pH – acidosis resulting from inability to retain HCO3- – oral NaHCO3 tablets to treat
Anaemia – decreased secretion/sensitivity to EPO leading to loss of RBC production
Also an element of haematuria in severe cases
Some general symptoms also seen: Breathlessness (anaemia) Seizure (uraemia?) Aches and pains (uraemia?) Nausea and vomiting Itching (uraemia)
Measurement of renal function – uses two main methods
Inulin clearance – give an IV infusion of inulin and because you know its freely filtered and isn’t secreted/reabsorbed you can measure amount in urine and calculate the true GFR (
eGFR – in reality, inulin is expensive and time consuming, so we use the patient’s creatinine levels as a cheap and pretty good approximation
Use plasma creatinine and an iPhone app to calculate
Importantly, the app adjusts the formula for age (GFR declines w/ age), race (black people have higher muscle mass) and gender (males have higher GFR)
Not perfect; only valid for adults, can’t show AKI only CKD and some decline in GFR gives normal creatinine levels (generally>50%)
How to Identifying cause of CKD
Context of a Past medical history (PMH )is vital, usually gives the game away
Many blood tests available for various causes; immunoglobulin (IgA nephropathy), ANCA (vasculitis/lupus), CRP (infection) etc.
Imaging to look for pathology (particularly obstructive/polycystic)
USS – hydronephrosis secondary to obstruction
CT – renal artery stenosis/aneurysm
Nutcracker syndrome is a rare condition where the left renal vein is compressed between the ‘nutcracker arms’ that are the abdominal aorta and the superior mesenteric artery. This venous congestion gives rise to CKD
MRI – renal artery stenosis/aneurysm
Treatment/management of CKD
Modify lifestyle factors – smoking, obesity and lack of exercise
Treat comorbidities – mainly diabetes and hypertension
Treat underlying pathology if possible
Reduce lipid intake/amount (statins)
ACEis if proteinuria shown (decrease the amount of this leads to better prognosis and also lowers BP leading to decreased hypertensive damage leads to better prognosis)
End of the line – dialysis or renal transplant
End stage renal disease (ESRD) definition
Defined as a level of renal function that would cause death without intervention (generally speaking, GFR
End stage renal disease (ESRD) Symptoms
symptoms are classified by loss of the kidney’s functions (like an exaggerated version of CKD):
Tiredness/fatigue/difficulty sleeping/difficulty concentrating (combination of anaemia and inability to excrete toxins)
Volume overload (similar to CHF; raised JVP, SoB, oedema etc.) due to inability to excrete fluid
Anaemia (see CKD, same pathology)
Bone disease (see CKD, same pathology)
Acidosis (see CKD, same pathology)
Uraemic symptoms (see CKD)
Also results in an increased sensitivity and narrowing of therapeutic index of many drugs due to decreased metabolism and or excretion
End stage renal disease (ESRD) Treatment
Falls under the umbrella term of renal replacement therapy
Haemodialysis – uses creation of an arteriovenous fistula (increases blood flow as blood goes artery vein) to allow a point for withdrawal of 300mls of blood at a time (entire circulatory volume dialysed in theory)
This allows for exchange along an extracorporeal circuit that causes diffusion between sterile dialysis fluid and blood (w/ heparin to prevent clotting) across a semi permeable membrane, eliminating toxins within the blood
Advantages; less responsibility for own care, 4/7 days off from dialysis, known to be effective in long term
Disadvantages; arteriovenous fistulae can be ugly (cosmetic problem, like a bad varicose vein), limits travel, have to keep to specific appointment, can damage CVS due to vol change
Contraindications; failed vascular access, heart failure and coagulopathy (last two relative, they’re less likely to kill you than the renal failure)
Peritoneal dialysis – uses the peritoneum as the semi-permeable membrane (same guiding principle is the same as haemodialysis). The peritoneum is filled with dialysis fluid and the exchange with the ECF/blood vessels allows for elimination of toxins
Two main types, one involves 4-5 bag changes every day, one takes place overnight
Advantages; autonomy of care, less fluid/diet/travel restrictions than haemodialysis
Disadvantages; no days off, frequent changes, responsibility, indwelling catheter leads to peritonitis, hernia etc.
Contraindications; failure of peritoneum (leak, hernia etc.), patient/carer can’t connect bag (elderly), obese/dench (relative contraindication, about peritoneal size to body bulk ratio)
Kidney transplant – gold standard for renal replacement therapy. Kidney is plumbed in at iliac fossa rather than normal T11-L2 as it’s easy access to iliac vessels and bladder
Types of donor
Deceased after brain death
Decreased after circulatory death
Live donation (usually related but can be altruistic)
Advantages; pretty much entirely restores renal function, no repetitive treatment, lower mortality vs dialysis, good long term prognosis >10yrs
Disadvantages; risk of operative mortality, limited donor supply (average wait ~3yrs, and have to be matched on blood group and MHC/HLAs), life long immunosuppression leading to infection (and Cushing symptoms if steroid dose high enough), still not a permanent fix
Worth noting that elderly patients tend to survive just as long with palliative care for ESRD as they do on haemo/peritoneal dialysis
Decompression sickness (‘the bends’)
An increased partial pressure at below sea level leads to diffusion of nitrogen from lungs into blood. If the diver ascends too quickly the rapid change in pressure causes bubble formation (like opening a bottle of coke) and this causes extensive tissue damage and is very painful
Respiratory distress syndrome
A loss of surfactant leads to upsetting of Laplace’s law () as surfactant normally keeps surface tension in small bubbles low. This leads to alveolar collapse due to the pressure difference in different sized alveoli, which reduces surface area for gas exchange and leads to respiratory failure (Type 1 then eventually 2). Commonly occurs in premature babies, and the mum can be given steroid injections to stimulate surfactant generation if anticipated
Also occurs as a result of trauma – tricky to treat
Carbon monoxide poisoning
CO binds to haemoglobin and forms carboxyhaemoglobin. This variant of Hb can’t bind O2 and so O2 delivery to tissues suffers. If occurs acutely it can kill in sleep (faulty gas boiler for example), but chronic exposure causes headaches, confusion, nausea etc. Needs treating with hyperbaric O2 therapy as in very high concentrations O2 can displace CO and restore function of Hb
Pulmonary embolism
Thrombus from a site other than the lungs (common the deep veins of the leg e.g. popliteal) lodges in one of the arteries of the pulmonary tree. This leads to a V/Q mismatch in the section of lung the artery supplies, so the pO2 of the blood leaving that section is low and the pCO2 is high. The hypercapnia causes resp rate to increase. Blood is redirected to healthy lung and the Inc. resp rate meansthe pO2 is normal (Hb is 100% saturated at 13.3kPa) but pCO2 is low. Mixed venous blood (from healthy and infarcted lung) therefore has low pO2 but normal/low pCO2 (Type 1 resp failure, see below)
Real danger comes from sudden pulmonary hypertension which can cause mechanical shock due to RV failure in heart
Types of respiratory failure
Type 1
Type 2
Type 1 respiratory failure
pO2 low, pCO2 normal or low. Due to either a diffusion defect or V/Q mismatch
Diffusion defect – any factor of Fick’s law affected leading to difficulty of diffusion between capillary blood and alveolar gas
As CO2 diffuses 20x more readily than O2 (much higher solubility coefficient) then it’s no surprise pCO2 is relatively unaffected
Also, any initial hypercapnia/the hypoxia increases resp rate and excess CO2 is blown off so pCO2 may be lowered
Pulmonary oedema – fluid in the alveoli/interstitium, increases diffusion distance
Emphysema – decreased compliance of lungs hyperexpansion reduced SA for gaseous exchange
Pulmonary fibrosis – fibrous deposits between alveolus and capillary BM leading to increased diffusion distance
V/Q mimatch – see pulmonary embolism
Type 2 respiratory failure
pO2 low, pCO2 high. A result of ventilation dysfunction leading to an inability to change air and no CO2 removal or O2 delivery. More serious than Type 1. Not easily corrected physiologically as increased respiratory drive won’t remedy the situation (ventilation compromised already)
Decreased respiratory effort
Narcotics/head injuries/neurological deficit e.g. stroke (anything that impacts ability of respiratory centre)
Muscular dysfunction – anywhere from the brain to the NMJ (multiple sclerosis, Duchene’s muscular dystrophy, spinal cord lesion, myasthenia gravis etc.)
Chest wall defects (rigid structure makes it harder to move and the lungs harder to inflate)
Severe scoliosis/kyphosis (spinal conditions, see ClinicalConditionsESA2)
Severe pectum excavatum/carranatum
Flail chest (section of ribs detached from thoracic cage by multiple fractures – major trauma)
Tension pneumothorax
Increased compliance – severe pulmonary fibrosis (IPF, see below)
Extremely high airway resistance (such that almost no expiration is possible)
Severe life threatening asthma attack
Acute exacerbation of late stage COPD (already in Persistent hypoxia w/ CO2 retention)
Asthma definition
A reversible airway obstruction
Pathophysiology of asthma
Airway remodeling including Inc. ASM thickness, damaged epithelia/basement membrane as a result of chronic inflammation (TNFa, neutrophils, eosinophils and mast cells) due to a reaction to ordinary stimuli e.g. dust
ASM contraction increases airway resistance so less air expired initially (think Poiselle’s law in CVS)
Contraction of ASM caused by histamine and prostaglandin release in response to many stimuli (cold temperatures, dust, pet dander etc.)
Epidemiology/aetiology of asthma
1/11 kids affected (1/12 adults, generational increase due to lifestyle conditions?)
Hygiene hypothesis – overuse of cleaning chemicals leads to reduced ‘training’ of immune system on harmless bacteria thus hyperactivity and atopy)
Sensitisation to allergens such as smoke, smog, fungal spores, dust etc. through priming of mast cells with IgE
Second exposure to the trigger causes IgE activation histamine release ASM contraction
Other (not allergic) types of asthma:
Viral asthma – disappears by ~5 years old
Occupational asthma – farmers etc.
Diagnosis of Asthma
History – can make the diagnosis on this ALONE – need two of the following:
Expiratory, polyphonic wheeze
Dry cough with diurnal variation (worse at night) – induced by exercise
Breathlessness (hypoxia leads to peripheral chemoreceptors increase respiratory drive)
Chest tightness
Variable airflow obstruction (reversed with B2 agonists)
Other things to note (increase suspicion but not used to confirm diagnosis):
Disturbance to life
Other aspects of atopy (hayfever and eczema)
Family history (of all atopic diseases)
Pets and passive smoke in the house
Intolerance to exercise
Examination Eczema Lethargy, uncomfortable at rest Below height for age, underweight?
Signs of labored breathing:
Harrison’s sulcus (indrawing of costal cartilages)
Tracheal tug
Subcostal recession
Obvious use of accessory muscles of inspiration (pec major, scalenes, sternocleidomastoid, serratus anterior etc.)
Investigation – diagnostic tools if unsure/monitor progress (particularly PEFR)
Primary PEFR – cheap and cheerful, reduced PEFR leads to obstructive airway disease Single breath (vitalograph) spirometry – measure FEV1:FVC (12% Inc. definitely asthma)
Supportive (optional)
FENO – patients w/ asthma have high levels of NO due to inflammation – can measure to give an idea of the level of inflammation
Skin prick – check sensitivity to common allergens and use to advise lifestyle changes
Chest X ray – exclude other differentials (only normally in acute exacerbations) e.g. pneumothorax, bronchitis
Treatment (long term) of asthma
Lifestyle – stop exposure to allergens (including passive smoking), exercise, fresh air etc.
Pharmacological (note inhalation all about eliminates off target side effects at the doses inhalers are used at)
Relievers – stave off acute exacerbations e.g. salbutamol (B2 agonist), ipratropium (Atreovent, M3 antagonist) and aminophylline (Inc. CAMP Inc. PKA Inc. SM dilation)
Preventers – low dose corticosteroids to suppress immune function locally
Treatment (asthma attack)
Recognition
Poor respiratory effort/loud wheeze/silent chest
Panicked, agitated, sympathetic features (sweating, dry mouth, dilated pupils, nausea etc.)
Altered GCS (cerebral hypoxia)
SaO2
Chronic obstructive pulmonary disease (COPD) definition
A progressive, worsening airway obstruction
Umbrella term for two pathologies
Chronic bronchitis – mucus hypersecretion and inflammation due to irritation by cigarette smoke
Cough chronically productive w/ frequent infections
Airway remodeling to Inc. ASM (as with asthma but different cause, result of chronic inflammation instead)
Emphysema – pathological destruction of terminal bronchioles and walls between alveoli
Inflammatory response to chronic irritation from cigarette smoke causes macrophages to release elastase and other proteolytic enzymes leads to breakdown of elastin
Forms large redundant bullae (‘superalveoli’) collapse on expiration due to loss of supportive tissue leading to obstruction
Fick’s law – less SA for diffusion leading to impaired gas exchange
Less elastin means less compliance and hyperinflation of lungs
Visible as Inc. rib spacing and width of thoracic cavity on CXR – ‘barrel chest’
Causes of COPD
SMOKING
A1-antitrypsin deficiency – hereditary, leads to overactivity of elastase leads to emphysema
Seen in young patients usually
Pollution (especially common in China)
Occupational e.g. coal worker’s pneumoconiosis
