Week 9 - Diseases of the Kidney and Urinary Tract Flashcards
Where are the kidneys located?
the retroperitoneum, mid-back; protected by lower ribs
The kidney’s are essential for life and receive approx. what percentage of blood supply from the heart?
25%
What is the function of kidneys?
-Filter blood into urine, excreting waste products
-Regulation of water, salt, calcium, phosphorus, blood pH, and others
-endocrine function
o Renin: regulation of blood pressure
o Erythropoietin: regulation of red blood cell production
o Regulates vitamin D metabolism
What are the 4 main microscopic components of the kidney?
- Glomerulus
- Tubules
- Interstitium
- Blood vessels
What is the functional unit of filtration?
Glomerulus (Glomeruli)
Describe the glomerulus
-Tuft of capillaries, with afferent (inward) and efferent (outward) arterioles
-Capillaries are lined by glomerular basement membrane (GBM)
-Surrounded by double lining of epithelial cells, called the Bowman’s capsule
-Bowman’s space is between the epithelial layers, and is also known as the urinary space
-The capillary endothelial cells contain fenestrations (sieve-like holes)
-Allows passage of fluid and small molecule (water, electrolytes)
-Restricts passage of larger molecules (proteins) and blood cells
-Glomerular basement membrane (GBM) surrounds endothelial cells
-Aids in filtration, as physical barrier, and charge barrier
-The GBM and endothelial cells are then surrounded by podocytes
-Podocytes contain foot processes with filtration slits
Describe filtration in the glomerulus
- Blood in capillary space passes through:
o Fenestrations in capillary walls
o Glomerular basement membrane
o Podocyte filtration slits - Fluid now in the urinary space (Bowman’s space) needs to be concentrated; enters the proximal convoluted tubule
Describe the urinary system
- Urine is emptied from collecting system into the renal pelvis
- Travels down the ureter into the bladder
- Exits via the urethra
- Renal pelvis, ureter, bladder is lined by urothelium
o 5-7 layers of epithelial cells
How is urine concentrated?
- From the renal corpuscle, fluid enters the proximal convoluted tubule
- PCT has resorptive and secretory abilities
o Specialized epithelial cells reabsorb about 2/3 of the filtered salt and water
o Also resorb other molecules (glucose, amino acids, potassium, urea, etc.) - Filtrate enters loop of Henle after proximal tubule
o U-shaped tube which creates concentration gradient in the kidney
o This allows further reabsorption of water and salt (across the gradient) - Filtrate enters distal convoluted tubule and then collecting ducts
What is the most common malignancy of the kidney?
Renal cell carcinoma
What percentage of adult cancers is renal cell carcinoma?
3%
What is the typical demographic for renal cell carcinoma?
Typically older patients (ages 50-60s) and more common in males (M:F ratio is 2:1)
What are the risk factors for renal cell carcinoma?
o Tobacco Smoking
o Obesity
o Hypertension
o Unopposed estrogen
o Exposure: asbestos, petroleum products, heavy metals
o Chronic kidney disease and acquired cystic disease
o Rarely can be related to syndrome/familial condition
What are the classic triad of renal cell carcinoma (presents in 10% of patients with larger tumours)
-Flank pain
-Palpable mass
-Hematuria (may be microscopic)
Describe the presentation of renal cell carcinoma?
- Classic triad
- May present with fever, feeling unwell, weakness, weight loss
- Most tumours are discovered incidentally by imaging
How is renal cell carcinoma treated?
Surgery - nephrectomy - partial or total (removal of kidney)
How does RCC present macroscopically?
yellow with areas of hemorrhage (red; photo of mass shown)
How is prognosis of RCC based?
On staging and tumour subtype
Is it uncommon for metastasis to be present when RCC is discovered?
No
What is the most common malignancy of the bladder?
Urothelial Carcinoma
What are the risk factors for urothelial cancer?
o Cigarette smoking (most important)
o Industrial exposure to some chemical compounds (aryl amines)
o Parasitic infection (Schistosoma haematobium)
Seen in endemic areas (Egypt, Sudan)
o Drugs - Long term analgesics, heavy long-term exposure to immunosuppressive drug
o Irradiation (usually many years later)
What is the typical demographic for urothelial cancer?
- More common in males (M:F ratio 3:1)
- More common in older patients (aged 50 to 80s)
Where does urothelial carcinoma arise?
urothelium (epithelium lining the urinary tract)
o May occur in renal pelvis or ureter
How does Urothelial Carcinoma present?
- Most often painless hematuria
- Sometimes urinary symptoms
o Urinary frequency
o Burning with urination
o Urinary urgency
UC can be Low grade or High grade, describe Low grade urothelial carcinoma
o Slow growing
o Papillary
o Minimal atypia
o Frequently recur
o Usually not aggressive
o Rarely invasive
UC can be Low grade or High grade, describe High grade urothelial carcinoma
o More aggressive
o May be flat or nodular
o High recurrence rate
o More atypical
o More likely to invade
o May metastasize
What is the treatment for urothelial carcinoma?
- For low grade, non-invasive, or minimally invasive tumours
o Local excision, often repeated numerous times as recurrence is common
o For more extensive tumours: intravesical chemotherapy or BCG - For high grade or muscle invasive tumours
o Cystectomy (resection of the bladder)
Describe pyelonephritis?
inflammation of the kidney - usually an infection of the kidney - it is a common disease affecting the kidney and can be divided into acute or chronic pyelonephritis.
Acute pyelonephritis is usually a _____ infection of the kidney
Bacterial
What are the symptoms of acute pyelonephritis?
o Fever
o Flank / back pain
o Nausea / vomiting
o Associated bladder infectious symptoms such as:
Pain with urination
Urinary frequency
Urgency
What is often the cause of acute pyelonephritis?
- Usually due to bladder infection
o Ascending infection
o May be due to obstruction or reflux - May be due to spread in the blood
o Hematogenous
What are the risk factors for acute pyelonephritis?
- Urinary tract obstruction
- Instrumentation (indwelling catheter)
- Vesicoureteral reflux
- Pregnancy
- Gender and age (often young females)
- Diabetes
- Immunosuppression / immunodeficiency
What is the treatment of acute pyelonephritis?
antibiotics (usually resolves)
How do you diagnose acute pyelonephritis?
urine culture, or urinalysis is also informative
How do you diagnose acute pyelonephritis?
urine culture, or urinalysis is also informative
Describe chronic pyelonephritis
Chronic inflammation and scarring of the kidney
What are the causes of chronic pyelonephritis?
o (Long term) Reflux
o Long term obstruction
o Recurrent infection
What are the typical ascending infectious agents responsible for acute pyelonephritis?
E. coli
Proteus
Enterobacter (all commonly found in bowel flora)
Describe acute renal failure
occurs over hours to days
- Can be reversible if underlying cause is treated
Describe chronic renal failure
occurs over prolonged time
- Progressive, irreversible destruction of kidney
- Loss of function
- May have no symptoms until late in disease course
List the causes of acute renal failure
Pre-renal: a process that results in decreased blood flow to the kidney
- Decreased BP (especially rapid)
- Dehydration
- Severe hemorrhage
Renal: process involving damage to the kidney
- Drugs, toxins, infection, inflammation, ischemic acute tubular injury, acute glomerulonephritis
Post-renal: obstruction of flow of urine
- Kidney stones
List the causes of chronic renal failure
Pre-renal
- Hypertension, diabetes, vasculitis
Renal
- Primary glomerular diseases
- Chronic tubulointerstitial disease
Post-renal
- Chronic urinary tract obstruction (enlarged prostate, malignancy)
What are the signs and symptoms/clinical presentation of renal failure?
- Azotemia (increased blood urea nitrogen [BUN] and creatinine)
- Edema / swelling
- Electrolyte disturbances
- Metabolic acidosis (low blood pH)
- Anemia (low hemoglobin)
- Hypertension
- Bone disease
Describe end stage renal disease
- Eventual end point of kidney diseases
o Especially if left untreated or poorly treated - Sclerosis of glomeruli
- Scarring/fibrosis of interstitium
- Loss of tubules (tubular atrophy)
- Chronic inflammation
- Thickened arteries
What is the treatment for renal disease?
- Lifestyle modification
o Balanced diet, avoid sodium, potassium, phosphate
o Exercise - Medication
o Control hypertension and diabetes
o Diuretics to help with fluid balance
o Specific medications to treat underlying kidney disease - Dialysis when kidney function declines to end stage renal disease
- Kidney transplant
Define renal disease
A condition in which the kidneys stop working and are not able to remove waste and extra water from the blood or keep body chemicals in balance.
Define glomerulopathy
Glomerulopathy is a set of diseases affecting the glomeruli of the nephron.
Describe diseases of the glomerulus (glomerulopathy)
- Important cause of renal disease
- Glomerular disease will affect the rest of the kidney
- Can be divided into primary and secondary glomerulopathies
- Results in damage to glomerular basement membrane
o Impairs filtration
Describe the mechanism of glomerular injury
- Most often due to abnormal immune mechanisms
o Antibodies reacting in situ within the glomerulus
o Deposition of circulating preformed antigen-antibody complexes within the glomerulus
Define primary glomerulopathies
affect the glomerulus alone or primarily
Define secondary glomerulopathies
systemic diseases (affect multiple organs), which affect the kidney
o ex. Diabetes, systemic lupus erythematosus, vasculitis
Describe the manifestations of glomerular injury
- Nephritic syndrome (hematuria, azotemia, variable proteinuria, oliguria, edema, hypertension)
- Nephrotic syndrome (proteinuria >3.5 g/day, hypoalbuminemia, hyperlipidemia, lipiduria)
What is the most common cause of acute renal failure (acute kidney injury)?
acute tubular injury/necrosis
Most forms of tubular injury also involve/affect what
the interstitium
What are the common causes of tubular injury/necrosis?
o Ischemia: decreased or interrupted blood flow
Often due to decreased blood volume
o Toxic injury to tubules
Endogenous agents: myoglobin, hemoglobin, monoclonal light chains, bile
Exogenous agents: drugs, radiocontrast dyes, heavy metals, organic solvents
Acute tubular injury/necrosis happens because tubule cells are sensitive to what?
ischemia and vulnerable to toxins
What is a major cause of end stage renal disease?
hypertension
Vascular diseases of the kidney are due to what?
- Atherosclerosis
o Narrowing of arteries due to plaque buildup
o Leads to decreased blood flow to the kidney
o Kidney atrophy
o Chronic kidney failure
o Risk of thromboembolism (clot), with renal infarct - Hypertension
o Major cause of end stage renal disease
o Leads to nephrosclerosis (sclerosis of renal arterioles, small arteries
o Scarring of glomeruli
o Chronic tubulointerstitial injury
o Decrease in renal mass
o Decline in renal function
What is the general clinical course for patients affected by ATI (acute tubular injury)
- Initial inciting event – medical or surgical event
- Decreased urine output
- Rise in BUN and creatinine
- Electrolyte abnormalities and metabolic acidosis
- Urine volume increases with recovery
o Loss of water, sodium, potassium as tubules are still damaged - Outcome related to magnitude and duration of ATI
- Most patients who survive initial event recover completely
Urine exits bladder via what?
urethra
Ureters and bladder are lined by what?
urothelium (5-7 layers)
What is urinary tract reflux called?
Vesicoureteral reflux (urine from bladder into ureters)
List the complications of vesicoureteral reflux
o Urinary tract infection, pyelonephritis
o Hydroureter/hydronephrosis
o Chronic renal failure (if advanced)
What is the cause of vesicoureteral reflux?
- May be due to anatomical defect (often congenital)
What is the treatment of vesicoureteral reflux?
o Conservative treatment: some cases will resolve as child grows
o Surgical reimplantation of ureter
What is the treatment for urinary tract stones?
- Wait for stone to pass
o Drink fluids
o Pain management - Lithotripsy (sound waves shatter stones)
- Surgical removal
Urinary tract stones are commonly called what?
kidney stones
Someone presents with abdominal pain and hematuria, what is the likely diagnosis and what will aid in diagnosing?
Urinary tract stones, and imaging (ultrasound, X-ray, CT scan)
Describe the presentation of someone with urinary tract stones
- May be asymptomatic
- May cause severe renal colic, abdominal pain
- May cause significant kidney damage
- Hematuria (blood in urine)
Urinary tract stones predispose patients to what?
infection
Most urinary tract stones form where?
kidney
Urinary tract stones are composed of what?
calcium oxalate/calcium phosphate (most common), struvite (magnesium ammonium phosphate), uric acid, cystine
Urinary tract stones affect who more commonly?
men more than women and those 20-30 years old
Urinary tract obstruction can be what?
- Intrinsic (lesions of urinary tract)
o Stones
o Congenital / acquired strictures
o Tumors of urinary tract
o Functional disorders (often neurogenic) - Extrinsic (external compression)
o Pregnancy
o Inflammation/scarring of surrounding organs
o Tumours in surrounding organs
What is the clinical presentation of someone with urinary tract obstruction?
- In acute obstruction, often have flank pain (renal colic)
- Unilateral/partial obstruction may be asymptomatic
o Unaffected kidney can maintain renal function - Chronic obstruction results in chronic kidney disease
- Predisposition to bacterial seeding and urinary tract infections
o Obstruction
o Urinary reflux
o Urinary stasis
