Exam 2: Renal and Urinary Tract Disease Flashcards
Overview
Kidney disease is classified by __
Cause
Causes of Kidney Disease
Pre-renal
Volume depletion (including sweat loss and hemorrhage)
Hypotension
Heart failure
stenosis
cirrhosis
NSAIDs
Causes of kidney disease
Intrarenal
Vascular (sclerosis, vasculitis)
Glomerular (membrane damage)
Tubular (cancer, toxic injury, altered ionic homeostasis
Causes of kidney disease
Postrenal
Obstruction
Stones
Prostatic disease
Pre-Renal Kidney Disease
Renal Artery Stenosis
Narrowing of at least one artery that supplies the kidneys
Pre-Renal Kidney Disease
What does Renal Artery Stenosis do to the kidneys?
Reduces blood flow and pressure into the kidneys
Activates renin-angiotensin system
cannot raise pressure within the kidney
Pre-Renal Kidney Disease
What causes the thickened tunica media in Renal Artery Stenosis?
Excess smooth muscle
fibrosis
Pre-Renal Kidney Disease
How is blood pressure regulated in the kidney?
Juxtaglomerular apparatus at vascular pole
Specialized JG cells produce renin
Macula densa cells detect ions
Pre-Renal Kidney Disease
What causes elevated arteriole pressure?
Higher glomerular filtration rate aters ionic concentration
Release of vasoactive compounds constricts arteriole, which decreases GFR
Lower NA+, Cl- concentration stops release
Pre-Renal Kidney Disease
How does a higher glomerular filtration rate alter ionic concentration in the kidney? How is it detected?
Less sodium and chloride can be recovered
Detected by cells in macula densa
Pre-Renal Kidney Disease
What does decreased arteriole pressure do in the kidneys?
Stimulates juxtaglomerular cells and release of renin
Pre-Renal Kidney Disease
Renin-Angiotensin System
JG cells release Renin from kidney
cleaves angiotensinogen into angiotensin I
Angiotensin-converting enzyme converts angiotensin I to angiotensin II
Angiotensin II causes vasoconstriction (decreased vascular space) in cardiovascular system and salt/water retention in kidneys (increases blood volume) - together increase BP
Pre-Renal Kidney Disease
What is the rate limiting step in the Renin-Angiotensin system?
Serum renin concentrations
System is controlled by JG cells in kidneys
Pre-Renal Kidney Disease
Where is angiotensin converting enxyme (ACE) found? How much Angiotensin II is converted in the kidneys?
Lung capillaries (also kidneys and other organs) express the enzyme
20% is converted
Pre-Renal Kidney Disease
Angiotensin II
Potent vasoconstrictor that directly increases blood pressure
Pre-Renal Kidney Disease
How does angiotensin II increase blood pressure? What does it do?
Stimulates adrenal glands to release aldosterone - promotes Na+ and water absorption in kidneys - increases blood volume - increases BP - increases BP shuts off renin release
Pre-Renal Kidney Disease: Renal Artery Stenosis
What are the symptoms of Renal Artery Stenosis?
High Blood Pressure (Renal HTN) (hyper tension in kidney, hypotension outside kidney)
Symptoms of Kidney Injury
Pre-Renal Kidney Disease: Renal Artery Stenosis
What are the causes of Renal Artery Stenosis?
Most common: athersclerosis
Less common: fibromuscular dysplasia
Decrease lumen - stenosis
Pre-Renal Kidney Disease: Renal Artery Stenosis
What are the treatments for Renal Artery Stenosis?
ACE inhibitors
Stent in renal artery/vessel
Intrarenal: Nephrosclerosis
Nephrosclerosis
Sclerosis of arterioles and small arteries within the kidneys
AKA Patchy atrophic ischemia
Intrarenal: Nephrosclerosis
What is the cause of Nephrosclerosis? What does it cause?
Caused by, and cause of, hypertension
Hylainization of vessel walls
genetics, age, general HTN
Intrarenal: Nephrosclerosis
What are the glomerular changes in Nephrosclerosis?
Partial to total sclerosis
GBM damage, collagen in Bowman’s space
Fibrosis around capsule
Intrarenal: Nephrosclerosis
What are the tubular changes in Nephrosclerosis?
Loss of tubules
Intrarenal: Nephrosclerosis
What is the result of vessel wall hyalinization in Nephrosclerosis?
Fibrin leaks through endothelium into vessel walls
Form smooths appearing eosinophilic membrane
Intrarenal: Nephrosclerosis
What are the clinical symptoms of Nephrosclerosis?
Unresolved HTM, diabetes increase risk of renal failure
Intrarenal: Nephrosclerosis
Does nephrosclerosis present with symptoms of clinical renal failure?
If nephrosclerosis is the only disease present, rare to present with symptoms of clinical renal failure
Intrarenal: Nephrosclerosis
Malignant HTN (unresolved HTN)
Endothelial damage results in protein leakage and development of clots
leads to renal ischemia (fibrinoid necrosis, hyperplastic arteriolitis)
Also frequent cause of renal failure in patients with sytemic sclerosis
Intrarenal: Nephrosclerosis
What effect does involvement of afferent arterioles have on unresolved HTN?
Leads to renin elevation
Intrarenal: Glomerular Damage
What are the causes of Glomerular Damage?
Secondary effects of systemic diseases
Circulating antigen:antibody complexes deposit in filtration membrane
Antibodies reacting against components of the filtration membrane
Intrarenal: Glomerular Damage
Primary glomerular disease starts in the…
Kidney
Intrarenal: Glomerular Damage
Where do immune complexes deposit?
- Podocyte effacement (between podocyte and their BM)
- Subepithelial deposits (In BM, but exterior to Lamina densa under podocytes)
- Subendothelial deposits (between endothelial cells and lamina densa)
- Mesangial deposits (mesangial membrane)
Intrarenal: Glomerular Damage
What disease is podocte effacement associated with?
Minimal change disease
Intrarenal: Glomerular Damage
What disease are subepithelial deposits associated with?
Membranous nephropathy
Intrarenal: Glomerular Damage
What disease are subendothelial deposits associated with?
Membranoproliferative glomerulonephritis
Intrarenal: Glomerular Damage
What disease are mesangial deposits associated with?
IgA nephropathy
Intrarenal: Glomerular Damage
What are the clinical consequences of glomerular damage?
Nephritic or Nephrotic Syndrome
Intrarenal: Glomerular Damage
Nephritic Syndrome
Glomerular inflammation
proliferative changes and leukocyte infiltration
Proteinuria and edema are less severe than nephrotic syndrome
Intrarenal: Glomerular Damage
Nephrotic Syndrome
Podocyte Injury
Immune or non-immune causes
Structural and/or physiochemical alterations
Damage to glomerular membrane - protein leakage
Intrarenal: Glomerular Damage
Compare and contrats Nephritic and Nephrotic Syndrome
Nephrotic: No hematuria, oliguria, hypertension
Both have proteinuria (lower level in nephritic)
Intrarenal: Glomerular Damage
What is the clinical presentation of Nephritic Syndrome?
Hematuria
Oliguria with azotemia
Proteinuria
Hypertension
Intrarenal: Glomerular Damage
What are the most common causes of Nephritic Syndrome?
Immunologically-mediated glomerular injury
Acute postinfectious glomerulonephritis
Rapidly progressive glomerulonephritis (RPGN) which often leads to crescentic lesions
Intrarenal: Glomerular Damage
What is the clinical presentation of Nephrotic Syndrome?
Massive proteinuria - depletes serum albumin
Hypoalbuminemia - low albumin reduces osmotic pressure of blood
Generalized edema due to reduced osmotic pressure and compensatory aldosterone secretion (hypovolemia)
Hyperlipidemia and lipiduria
Intrarenal: Glomerular Damage
What are the causes of Nephrotic Syndrome?
Minimal-change disease
Membranous Nephropathy
Intrarenal: Glomerular Damage: Nephrotic Syndrome
Minimal-change disease
Due to glomerular damage, leakage across filtraion membrane
Lipoproteins accumulate in proximal convoluted tubules (visible lipid droplets and protein accumulations)
somep odocyte effacement - causes nephrotic syndrome
Intrarenal: Glomerular Damage: Nephrotic Syndrome
Minimal-change disease is most common in…
children
Intrarenal: Glomerular Damage: Nephrotic Syndrome
Membranous Nephropathy
Diffuse thickening of capillary walls (Ig deposits or self-antibodies)
Ig activates complement
Attack on podocytes allows protein leakage
Sudden onset
Intrarenal: Glomerular Damage: Nephritic Syndrome
What are the causes of Nephritic Syndrome?
Post-Streptococcal Glomerulonephritis
Goodpasture Syndrome
Crescentic Glomerulonephritis
Intrarenal: Glomerular Damage: Nephritic Syndrome
Post-Streptococcal Glomerulonephritis
Antibodies to steptococcal proteins will recognize glomerular proteins
activation of complement causes infiltration of neutrophils and other leukocytes
Immune response will also induce proliferation of cells in glomerulus (increased cellularity of glomerulus, deposits in subendothelial space, membrane, subepithelial space)
Intrarenal: Glomerular Damage: Nephritic Syndrome
Goodpasture syndrome
Renal failure with pulmonary hemorrhage
Parietal epithelial cells can transdifferentiate to produce replacement podocytes (immune response causes necrosis in glomerulus)
Intrarenal: Glomerular Damage: Nephritic Syndrome
What causes Goodpasture Syndrome?
Antbodies against basement membrane components (Anti-GBM in kidney, which may recognize alveolar bm)
Anti-GBM antigen is in collagen IV; source of pulmonary hemorrhage
Intrarenal: Glomerular Damage: Nephritic Syndrome
What is the clinical presentation of Goodpasture Syndrome?
Hemoptysis
Hematuria
Nephritic (and possibly nephrotic) syndrome
Intrarenal: Glomerular Damage: Nephritic Syndrome
What is the treatment for Goodpasture Syndrome?
Plasmaphereis to remove antibodies
immunosuppression
Intrarenal: Glomerular Damage: Nephritic Syndrome
Crescentic Glomerulonephritis
Rapidly progressive glomerulonephritis (RPGN)
Crescents form due to proliferation of parietal cells of Bowman’s membrane (induced my macrophages, monocyte chemotaxis)
Intrarenal: Glomerular Damage: Nephritic Syndrome
Why is Crescentic Glomerulonephitis also known as rapidly progresisve glomerulonephritis?
Clinical syndrom - rapid loss of renal function
Intrarenal: Glomerular Damage: Nephritic Syndrome
What are the 3 types of Crescentic Glomerulonephritis based on? What are they?
Immunological mechanisms
1. Anti-GBM antibody mediated disease (Goodpasture Syndrome)
2. Immune complex deposition (lupus)
3. Anti-neutrophil cytoplasmic antibodies (ANCAs) (idiopathic, systemic vasculitis)
Intrarenal: Tubular Damage
Tubulointerstitial nephritis
Inflammation(nephritis) of interstitium (interstitial) and tubules(tubulo)
Intrarenal: Tubular Damage: Pathways of Renal infection
Acute Pyelonephritis
Bacterial infection due to UTI
Intrarenal: Tubular Damage: Pathways of Renal infection
Chronic Pyelonephritis
History of UTI
Fibrosis of pelvis and calyx
Intrarenal: Tubular Damage: Pathways of Renal infection
Drug-induced inflammation
Edema and mononuclear infiltrate into interstitium
Penicillin derivatives, other antibiotics, NSAIDs, others
Intrarenal: Tubular Damage
Ionic Homeostasis
Balance between cations and anions
Intrarenal: Tubular Damage
What is the purpose of Ionic Homeostasis?
maintain pH around 7.4
Concentrationsof ions maintain osmolarity
Ions necessary for function maintained at correct concentration
Intrarenal: Tubular Damage
Exretion must be _ by intake to maintain balannce
matched
Intrarenal: Tubular Damage
How much of your body weight is body water? What is it comprised of?
60% of body weight
breaks down to:
* 20% bw is ECF
* 40% bw is ICF
Intrarenal: Tubular Damage
What is the ECF? What are the major cations and anions?
Plasma + interstitial (filtrate of plasma; no cells or large proteins) (Extracellular fluid)
Cation: Na+
Aniona: Cl- and HCO3-
Intrarenal: Tubular Damage
What is the ICF? What are the major cationd and anions?
Intracellular fluid
Cations: K+ and Mg2+
Anions: proteins and organic phosphates (ATP, ADP, AMP)
Intrarenal: Tubular Damage
Water Intoxication
Water poisoning/Fatal hyponatremia
Drink so much water it becomes toxic - kidney cant remove fluid fast enough
Urine excretion can be increased to 16 mL/min (usually 1 ml/min) when large quantities of hypotonic fluid are ingested
If ingestion exceeds this, or continues for too long, cells will swell due to water uptake to cope with Hypotonic ECF
Intrarenal: Tubular Damage
What are the symptoms of water intoxication?
Swelling of CNS neurons
Convulsions, coma (can kill)
Kidney Injury
What is the most common cause of acute renal failure? Why?
Acute Kidney Injury
Rapid reduction of renal function, including output <400 ml/day (oliguria to anuria)
50% of acute renal failure occurs in hospital patients
Kidney Injury
What evidence could you find of tubular injury?
glomerular, interstitial, vascular injury
Kidney Injury
What are the causes of Acute Kidney Injury?
Ischemia
Direct Toxic Injury
Inflammation
Urinary Obstruction
Kidney Injury
What causes ischemia in AKI?
Malfunction of intrarenal blood vessels
Thomboses
Decreased blood volume
Kidney Injury
What causes urinary obstruction in AKI?
Tumors, prostatic hypertrophy, blood clots
Kidney Injury
Pathogenesis of AKI
Tubule Cell injury (Toxic/Ischemic Injury)
Distrubed Blood flow
Kidney Injury
Tubule Cell Injury: Toxic Injury
Cells are more sensitive due to higher metabolic requirements, high absorption rates, and concentration capacity
Kidney Injury
Tubule Cell Injury: Ischemic Injury
Tubules cells are more sensitive to lack of nutrients
ischemia causes vasoconstriction
Kidney Injury
Disturbed Blood Flow
Hemodynamic alterations affect GFR
Kidney Injury
What is the treatment for AKI?
Prevent further damage (address cause)
Antibiotics - prevent secondary infections
Diuretics - flush out the kidneys
Dialysis
Kidney Injury
How is the damage distributed in AKI?
Proteins, lipids, blood cells acculate on the inner aspect of the tube
Form casts that can be passed into the urine
Necrosis occurs in areas most impacted by damage
Kidney Injury
How do you differentiate the connvoluted tubules?
DCT: Less esosinophilic
PCT: Visible brush border
Both: Cuboidal Cells
Chronic Kidney DIsease
What is the difference between Chronic Kidney Disease and AKI?
Chronic Kidney Disease: Irreversible loss of tubular cells
AKI: can resolve through regeneration
Chronic Kidney DIsease
What is the cause of chronic kidney disease?
Most common cause is diabetes mellitus
Other common causes include hypertension and glomerulonephritis
endpoint of all chronic renal parenchymal diseases
Chronic Kidney DIsease
What are the markers of kidney damage?
Alterations in blood
urine composition
Chronic Kidney DIsease
What is the treatment for Chronic Kidney Disease?
Address underlying cause
Changes in diet, lifestyle to prevent damage
Serious: Dialysis, transplant
Chronic Kidney DIsease
Chronic Kidney Disease
Irreversible loss of tubular cells
Significntly decreased GFR and/or albuminuria for 3 months
Chronic Kidney DIsease
What are the clinical manifestations of kidney damage?
altered kidney functions that affect:
* Sodium and potassium homeostasis
* Water balance
* Acid-base balance
* Urea excretion
Chronic Kidney DIsease
How does kisney damage affect sodium potassium homeostasis?
Excess Na+ expands intravascular volume
Hypertension and congestive heart failure
Chronic Kidney DIsease
How does kidney damage affect urea excretion?
Reduced excretion increases BUN and serum creatinine, produces uremia
BUN = blood urea nitrogen
Chronic Kidney DIsease
What are clinical symptoms of kidney damage?
Dehydration, edema, hyperkalemia
Hyperphosphatemia, hypocalcemia, bone/parathyroid effects
anemia
Hypertension, congestive heart failure, cardiomyopathy, pulmonary edema, uremic pericarditis
Nausea and vomiting, GI bleeds, inflammation of the esophagus, stomach, colon
Skin: sallow, pruritic, dermatitis
Kidney Damage
Uremia
Increases levels of urea in the blood
Kidney Damage
What are the symptoms of Uremia?
Decreased appetite
Fatigue
Neurological symptoms (confusion, coma)
Skin excretion (uremic frost)
Kidney Damage
What causes uremia?
Accumulation of nitrogenous waste products due to kidney failure
Hypotension
dehydration
trauma (increased protein catabolism)
Kidney Damage
What are other consequences of Uremia?
Kidneys no longer activate vitamin D
Necessary for calcium/phosphate absorpion
Renal Osteodystrophy
Renal Osteodystrophy
Lack of vitamin D reduces intestinal Ca2+ absorption
Renal Osteodystrophy
What is the mechanism of Renal Osteodystrophy?
Low plasma Ca2+ causes parathyroid hyperplasia
PTH increases oteoclast activity
Secondary hyperparathyroidism causes bone calcium depletion
Obstructive Uropathy
What are the most common sites of Kidney Stones?
Collecting system
Renal pelvis and calcyes
Obstructive Uropathy
What are the causes of kidney stones?
Genetics
Dehydration
Dietary Intake
Hormonal imbalance (parathyroid tumor)
Obstructive Uropathy
What are the 4 types of kidney stones?
Calcium (75%)
Uric Acid (<10%)
Cystine (1%)
Infection (15%)
Obstructive Uropathy
Kidney Stones: Calcium
75% of kidney stones are calcium
oxalate and/or phosphate salts
Obstructive Uropathy
Kidney stones: Uric Acid
<10% of kidney stones
25% of gout/hyperuricemia patients
most are idiopathic
Obstructive Uropathy
Kidney Stones: Cystine
1% of kidney stones
Children with hereditary cystinuria
Obstructive Uropathy
Kidney Stones: Infection
15% of kidney stones
Bacteria cleave urea
* Proteus or providencia species
* produces ammonia - caused urine to become alkaline - favors salt deposition - Struvite NH4MgPO4.6H2O - apatite Ca5(PO4)3(OH)2
Obstructive Uropathy
What are the consequences of the obstruction of kidney stones?
Damage typically seen in tubules
Causes increased intrarenal pressure (will damage tissue, infection or abscess can occur behind stone)
Hypertension due to renin production
Obstructive Uropathy
What causes pain from kidney stones?
Due to distension of renal capsule, renal pelvis or ureters
Damage to these structures can cause ureters
Obstructive Uropathy
Hydronephrosis
Expansion of pelvis and calcyes due to obstruction in ureters or further out
Urine backs up into kidneys
Obstructive Uropathy
What causes hydronephrosis?
Calculus can block ureters
Will compress parenchyma and damage it (tubules first, then glomeruli; atrophy and fibrosis)
Obstructive Uropathy
Hydronephrosis: Unilateral Blockage
Blockage in ureter
Obstructive Uropathy
Hydronephrosis: Bilateral blockage
Blockage in bladder or urethra
Obstructive Uropathy
How do you treat kidney stones?
Pain magement
Prevent dehydration (water and other fluids)
Use shock waves to break up the stone
Stent in ureter to maintain patency
Prevent new stones from forming (depends on type of stone)
Obstructive Uropathy
How can allopurinol be used to treat kidney stones?
Inhibits purine catabolism to reduce uric acid production
Postrenal
Actue cystitis
Neutrophil infiltrate
Inflammation of bladder
Postrenal
Chronic Cystitis
Mononuclear infiltrate (macrophages and T cells)
Inflammation of bladder
Postrenal
Types of cystitis (bladder inflammation)
Bacterial infection (or viral)
Hemorrhagic
Interstitial
Malakoplakia
Polypoid
Postrenal
Hemorrhagic cystitis
Side-effect of cytotoxic chemotherapeutics
can be due to adenovirus infection
Postrenal
Interstitial Cystitis
Pain when bladder fills
Other symptoms: Urgency, hematuria, dysuria
Postrenal
Malakoplakia Cystitis
Defects in phagocytic cells (undigested bacterial components accumulate)
Postrenal
Polypoid Cystitis
May look like papillomatous cancer but due to submucosal edema
Postrenal
What are the most common species to cause Cystitis?
E. coli (most common), Proteus, Klebsiella, Enterobacter
Postrenal
What are the predisposing factors of cystitis?
Bladder stones
Obstruction
Diabetes mellitus
Immune defificency
Postrenal
What are the triad of symptoms of cystitis?
- Frequency (up to every 15-20 minutes)
- Lower abdominal pain
- Dysuria (pain/burning upon urination)
