Renal Pathophysiology Flashcards
Kidney structure
Physiological Function of Kidneys
-endocrine functions
-excretion
-control solutes/fluids
-control BP
-acid/base balance
Glomular Filtration depends on
-GFR
-size of drug
-extent of plasma protein binding (only unbound is unfiltered)
Renal drug excretion
-slide 8 structure
-major route of elimination for 25-30% of drugs
renal anatomy
-Bowman’s capsule
-Proximal Tubule
-Loop of Henle
-Distal Tubule
-Collecting Tubule
-most H20 and solutes reabsorbed
-concentrate waste
Bowman’s capsule
-100% filtrate produced
Proximal Tubule
-80% reabsorbed
-active and passive absorption
-secretion and reabsorption of organic acids and bases (**uric acid and most diuretics)
Loop of Henle
-6% reabsorbed
-H2O (descending) and salt conservation (ascending)
-active reabsorption of Na, K, Cl
-2’ reabsorption of Ca and Mg
Distal tubule
-9% reabsorbed
-variable reabsorption
-active secretion
-parathyroid hormone control
Collecting Tubule
-4% reabsorbed
-variable salt and H20 reabsorption
-water reabsorption under vasopressin
Key physiolofical flow values??
??
Anatomical Solute and Water Flux in nephron
Measures of Kidney Function
-Serum Creatinine
-Blood Urea Nitrogen (BUN)
-Creatinine Clearance
-GFR
Serum Creatinine
-mostly removed by filtration
-increase is bad
Blood Urea Nitrogen (BUN)
-measure of waste from liver breakdown of AAs
-increase is bad
Creatinine Clearance
-predicts secretion and drug clearance
Markers of Kidney Damage
-urinary abnormalities (protein, RBC suggestive of membrane malfunctions)
-imaging abnormalities (MRI/CT scans)
Aging Kidney
-decline in kidney mass = decline in function
-prob gotta lower the dose slide 14
Compensatory response to renal injury
- injury
- decrease of nephrons
- compensatory inc in size and function of remaining nephrons
- glomerular/tubular lesions
- Loss of nephrons greater than compensatory capacity
- progressive decrease in GFR
- Azotemia
- Uremic Syndrome
9.Death
Sources of kidney injury/failure
-HTN and Diabetes >60%
-glomerulonephritis
-cystic kidney
-other urologic diseases (stones)
impact of acute kidney failure
-300,000 deaths per year in US (more than breast cancer, prostate. cancer, heart failure, and diabetes combined)
Pathophysiology of Acute Kidney Failure
-inc in SCr 0.3mg/dL or more within 48hours
OR
-50% inc in SCr within the last 7 days
OR
-reduction in urine output
Classification of Major causes of acture kidney injury
-prerenal
-intrinsic
-postrenal
Prerenal causes of AKI
-hypovolemia
-dec cardiac output
-dec circulation
-impaired renal autoregulation (NSAIDs, ACE-I/ARB, cyclosporine)
Intrinsic sources of AKI
-acute glomerulonephritis
-ischemia, sepsis/infection, nephrotoxins in tubules
-vasculitis, HTN, TTP-HUS (vascular)
Postrenal sources of AKI
-bladder outlet obstruction
-bilateral pelvoreteral obstruction
Normal perfusion pressure
-normal glomerular capillary pressure is maintained by afferent vasodilation and efferent vasoconstriction
Decreased perfusion rate
-inc vasodilatory prostaglandins
-inc angiotensin II
-maintain normal glomerular capillary pressure
Reduced perfusion pressure in the presence of NSAIDs
-dec vasodilatory prostaglandins
-inc angiotensin II
=inc afferent resistance
=GCP and GFR dec
Decreased Perfusion pressure w ACE-I or ARB (angiotensin inhibitor)
-slight inc vasodilatory prostaglandins
-dec angiotensin II
=dec efferent resistance
=GCP and GFR drop
Kidney and ureter obstructions
-stones
-clots
-external compression
-tumor
-fibrosis
Bladder obstruction
-prostate enlargement
-blood clots
-cancer
Urethra obstruction
-strictures
-obstructed Foley catheter
Pathophysiology of CKD (key elements)
-inc GCP
-proteinuria
-glomerulosclerosis
CKD-MBD
CKD-MBD causes
-impaired phosphate excretion
-dec vit D3 production
Kidneys and Vit D metabolism
-managing CKD requires dealing with Ca homeostasis
-mineral bone disorder maybe
Uremia
-accumulation of waste usually cleared by kidneys
Symptoms of Uremia
-fatigue
-neuropathy
-seizures
-nausea
-ammenorrhea
-bone disease
-insulin
-itching
-anemia
Specific Nephropathies
-NephrItic Syndrome
-NephrOtic Syndrome
-cycstic disease
-nephrolithiasis
-contrast-induced nephropathy
NephrItic Syndrome
-Inflammation disrupting glom membrane
-hematuria (dark urine)
-RBC casts
NephrOtic syndromes
-pOdcyte damage that disrupts charge-barrier of glom
-massive prOteinuria
-more edema
-low serum albumin
Glomerulonephritis
-inflammation of glomeruli
-acute or chronic
-proteinuria or hematuria
Glomerulonephritis causes
1’: inheritable (Alport Syndrome)
2’: infections, drugs, auto-immune disorders (vasculitis, Lupus)
Pathogenesis of Glom disease
-Immune
1. Antibody-associated injury
2. Cell-mediated immune
3. Other mechs of injury
Pyelonephritis
-inflammation of kidney tissue
-acute or chronic
-flank pain
-painful pissing
-bacteria from blood or urinary tract
-WBC in urine
-could lead to sepsis
UTI patho
-colonize urethral area and acesnds
-fimbria allow bacteria to attach and penetrate
-replicate and may form biofilms
Interstitial Nephritis
-primary injury to renal tubules
-indetected until sig dec in renal function
Causes of interstitial nephritis
-drugs (75%) mostly antibiotics
-infection
-autoimmune
Drugs associated w AIN
-PENICILLINS
-abx (cephalosporins, sulfa)
-diuretics (thiazide, furosemide)
-NSAIDs
-anticonvulsants (phenytoin, carbamazepine, phenobarbital)
-allopurinol, cimetidine
Cystic Diseases of the Kidney
-simple cysts
-autosomal dominant polycystic kidney disease (adulthood)
-autosomal recessive polycystic kidney disease (childhood)
Simple Cysts
-most common cystic renal disease
-NOT tumor
Autosomal Dominant Polycystic Kidney Disease (APKD)
-expanding cysts that destroy the intervening parenchyma
-adulthood
APKD
-inherited mutation of PKD1 or 2 in renal tubular cells
-abnormal cysts form
-destroy intervening parenchyma
-intermittent gross hematuria (blood in urine)
-HTN and UTI end up being fatal
-need renal transplant
Autosomal Recessive polycystic kidney disease
-autosomal recessive inheritance
-mutation in PKHD1 (fibrocystin)
-present at birth
-infants die fast from pulmonary/renal failure
-if survive, develop liver cirrhosis (congenital hepatic fibrosis)
Nephrolithiasis
-kidney stones
-10% of men 5% of women
-arises from supersaturation of solutes
-esp calcium
Renal Calculi (kidney stones)
-males over 40 esp
-N/V
-flank pain, sharp and sudden
-hematuria
Promoters of kidney stones
-sodium intake
-calcium intake
-high acid intake
Inhibitors of kidney stones
-Citrate
-Magnesium
Non-infection kidney stones
-calcium
-uric acid
Infection stones
-Struvite
-alkalized urine from UTI
Genetic Stones
-Cystine
-defective transporter
-tx w alkaline citrates
Primary treatment of kidney stones
-analgesics
-hydration
-lithotripsy
-surgery
Prevention of kidney stones
-diet (eliminate Ca)
-hydration
-diuretics
Contrast-Associated Nephropathy
-25% inc in SCr within 72 hours of contrast media admin
-CIN causes 1/3 of hospital acquired AKI
-1-2% US
-hydrate and avoid nephrotoxins
Contrast-Associated Nephropathy patho
-contrast media
=cytotoxicity or inc viscocity
=dec perfusion
=medullary ischaemia
or dec GFR
When may NSAIDs be appropriate in patients with acute heart failure and chronic kidney disease?
-Never
Risk of NSAIDs in heart failure and CKD
-sodium retention
-fluid overload
-acute kidney injury
-hyperkalemia
