PATHO - Urinary System

Question 1

Functions of renal system

Answer 1

• maintain stable internal environment for optimal cell and tissue metabolism (via solute and water transporting and balance)
• endocrine function - secretes renin (for BP), erythropoietin RBC production), and 1,25- dihydroxy-vitamin D3 (for calcium metabolism)
• release glucose into the circulation by the processes of glycogenolysis and gluconeogenesis

Question 2

Outer Structure and Location of Kidney

Answer 2

Structure: paired organs in posterior region of abdominal cavity (retroperitoneum). Lie on either side of vertebral column, upper and lower poles go from T12 to L3.

• R kidney slightly lower and displaced downward by overlying lvier
• each kidney ~11cm long, 5-6cm wide, 3-4cm thick
• surrounded by the renal capsule which is embedded in perirenal fat. These layers are further covered with a double layer of renal fascia (fibrous tissue).
• Position of kidney and layer of fat is for protection
• Hilum: indentation in the middle of the kidney, where everything enters/exits (renal blood vessels, nerves, lymphatics, and ureters)

Question 3

Inner structure of kidney

Answer 3

• Cortex: outer layer of kidney - contains all the glomeruli, most of the proximal tubules and some segments of distal tubule
• Medulla: inner part of kidney and consists of pyramids regions (pyramids extend into renal pelvis and contains loops of Henle and colleting ducts)
• Renal columns: extension of the cortex, extends between the pyramids to the renal pelvis
• Minor and major calyces: chambers receiving urine from collecting ducts and form entry into the renal pelvis (which is an extension of upper ureter)
• Structural unit of kidney: lobe - each composed of a pyramid and overlying cortex (~14-18 lobes in each kidney)

Question 4

Functional unit of the kidney is the ____________.

Answer 4

nephron

Question 5

Structural composition of nephron

Answer 5

• tubular structure with subunits (renal corpuscle, proximal convoluted tubule, loops of Henle, distal convoluted tubule, collecting duct)
• ~1.2 million nephrons in each kidney

Question 6

What are the three kinds of nephrons in the kidney?

Answer 6

1) superficial cortical nephrons: 85% of nephrons, extend partially into the medulla

2) midcortical nephons: has short or long loops

3) juxtamedullary nephrons: ~12% of nephrons which lie close to and extend deep into the medulla (~40mm); important for concentration of urine

Question 7

Composition of the renal corpuscle

Answer 7

1) Glomerulus: tuft of capillaries that loop into the Bowman capsule (like fingers pushed into bread dough). Blood supply from afferent arteriole, drained by efferent arteriole.

2) Bowman capsule/space

3) Mesangial cells: shaped like smooth muscle cells; secrete mesangial matrix (type of connective tissue) and lie between and support capillaries. Also have phagocytic abilities simliar to monocyes, release inflammatory cytokines, and can contract to regulate glomerular capillary blood flow.

Question 8

Glomerular Filtration Membrane - Structure and Function

Answer 8

Structure: 3 layers

• 1) inner capillary endothelium - made of cells in continuous contact with basement membrane and has pores.
• 2) middle basement membrane - selectively permeable network of glycoproteins and mucopolysaccharides
• 3) outer layer capillary epithelium - made of podocytes which are cells that have foto porjections that stick to the basement membrane. Also interlocks with neighbouring podocytes to create filtration slits

Function: filters blood components through its three layers. Separates the blood of glomerulr capillaries from fluid in Bowman space to allow filtration to occur (with the exception of blood cells and plasma proteins with a high MW). Filtrates passes through and finally becomes primary urine.

Question 9

Structure and function of the juxtaglomerular apparatus

Answer 9

Structure:

• composed of juxtaglomerular cells (which release renin)
• and macula densa (sodium-sending cells) of the distal tubule which is between the afferent and efferent arterioles

Function: control of renal blood flow, glomerular filtration, renin and secretion

Question 10

Structure of proximal convoluted tubule

Answer 10

• starts from the Bowman space and has an initial voncoluted segment (pars convoluta) and then straight segment (pars recta) that descends towards medulla
• wall made of one layer of cuboidal epithelial cells with surface layer of microvilli (brush border) that increases reabsorptive SA
• then joins Loop of Henle
• brush border and high number of mitochondria in cells of PCT promote reabsorption of 50% of glomerular filtrate

Question 11

Structure of loop of Henle

Answer 11

• extends into medulla
• cells of the thick segment part of the loop are cuboidal and actively transport several solutes (not water)
• thin ascending segment of the loop narrows and made of thin squamous cells with no active transport function

Question 12

Structure of distal tubule

Answer 12

• has straight and convoluted segments
• extends from macula densa to collecting duct which is a large tubule that descends down the cortex and through the renal pyramids in the inner and outer medullae (which draines urine into minor calyx)
• composed of:
  
  • principal cells: reabsorb sodium and secrete potassium
  • intercalated cells: secrete H+ and reabsorb K+ and bicarbonate

Question 13

What are the major blood vessels of the kidney?

Answer 13

1) Renal arteries
2) Interlobar artery
3) Arcuate arteries
4) Glomerular capillaries
5) Peritubular capillaries
6) Vasa recta
7) Renal veins

Question 14

Where do renal arteries originate and end?

Answer 14

Originate: as 5th branches of abdominal aorta, dividing into anterior and posterior branches at renal hilum, subdivide into lobar arteries

End: lower, middle, and upper thirds of kidney

Question 15

Structure of interlobar artery

Answer 15

subdivisions travel down renal colummns and between pyramids, form afferent glomerular arteries

Question 16

Structure of arcuate arteries

Answer 16

made of branches of interlobar arteries at cortical-medullary junction and arches over the base of pyramids and run parallel to the surface

Question 17

Structure of glomerular capillaries

Answer 17

• made of 4-8 vessels, arranged in a fistlike structure
• arise from afferent arteriole, empty into efferent arteriole which carries blood to the peritubular capillaries
• major vessels that regulate intrarenal blood flow

Question 18

Structure of peritubular capillaries

Answer 18

• surround convoluted portions of the proximal and distal tubules and loop of Henle
• adapted for cortical and juxtamedullary nephrons

Question 19

Structure of vasa recta

Answer 19

• network of capillaries that forms loops, closely follows loop of Henle
• the only blood supply to the medulla (important for formation of concentrated urine)

Question 20

Structure of renal veins

Answer 20

• goes in the reverse direction of the arteries
• eventually empties into IVC

Question 21

Flow of urine

Answer 21

formed by nephrons & flows from distal tubules and collecting ducts through papillary ducts to the renal papillae (projections of the ducts) into the calyces, where it is collected in the renal pelvis and then funneled into the ureters

Question 22

Describe the structure & innervation of the ureters, and flow of urine through the ureters

Answer 22

Structures:

• ~30cm long, made of long intertwining smooth muscle bundles
• lower ends of ureters pass obliquely through the posterior aspect of the bladder wall
• Sympathetic imput at upper part of ureter (T10 nerve roots) with referred pain to umbilicus
• Parasympathetic sacral nerves innervate lower part of ureter with referred pain to vulva/penis
• Primary arteries for blood supply from kidney, some from lumbar/superior vesical arteries

Flow of urine mechanism:

• smooth muscle cells are nearby to allow electrical stimulation from one cell to another and cause downward peristalsis contraction of urine into the bladder
• Contraction of bladder during micturition compresses lower end of ureter to prevent reflux
• Peristalsis maintained even is ureter is denervated

Question 23

Structure of bladder

Answer 23

Structure: bag of smooth muscle that forms the destrusor muscle and smooth uroepithelium lining. Uroepithelium forms the interface between urinary space and underlying vasculature and connective/nervous/muscle tissue.

• when bladder fills with urine, distension occurs and the layers of uroepithelium slide past each other to become thinner and bladder volume increases
• contains an smooth triangular area (aka trigone) that’s between the openings of the two ureters and urethra
• has a profuse blood supply; innervated by parasympathetic fibers
• position varies with age and sex

Question 24

Function of uroepithelium

Answer 24

• allows for the bladder wall to expand when it fills
• lines the urinary tract from renal pelvis to urethra
• acts as a barrier to prevent movement of water and solutes between urine and blood
• communicates information about urine pressure and composition to surrounding nerve and muscle cells

Question 25

Structure of urethra

Answer 25

Structure: tube that allows urine to pass out of the body. Extends from inferior side of bladder to the outside of body. Lined with mucus-secreting glands.

• contains ring of smooth muscle (internal urethral sphincter) at urethra and bladder junction; internal sphincter innervated by parasympathetic fibers
• External urethral sphincter made of striated skeletal muscle, under voluntary control
• Female’s: short (3-4cm)
• Male’s: long (18-20cm) and has 3 segments

Question 26

What are the three segments of the male urethra?

Answer 26

• prostatic: closest to the bladder. passes through the prostate gland and contains openings of the ejaculatory ducts
• membraneous: passes through the floor of the pelvis
• penile: forms the remainder of the tube
• all surrounded by corpus spongiosum erectile tissue and contains openings of the bulbourethral mucous glands

Question 27

Describe the reflex arc for micturition.

Answer 27

• stimulated by mechanoreceptors that respond to stretching of tissue (sensing bladder fullness)
• sends impulses to sacral level of the cord
• when bladder accumulates 250-300mL of urine, bladder contracts and internal urethral sphincter relaxes through activation of spinal reflex arc (micturition reflex)
• person then feels urge to void
• Then finally voluntary control of micturition can occur by relaxing/contracting external sphincter

Question 28

How much blood does the kidney receive per minute?

How much plasma is flowing through the kidney per minute?

Answer 28

1000-1200mL of blood/min (20-25% of the cardiac output)

~600-700mL of blood/min is plasma that’s flowing through kidney

Question 29

From the renal plasma flow (RPF), how much is filtered at the glomerulus and passes into Bowman capsule? Where does the rest of the plasma flow?

Answer 29

20% (~120-140 mL/min) of plasma flows through glomerulus into Bowman capsule. ~102ml/min of glomerular filtrat is reabsorbed from nephron tubules and returned to circulation via peritubular capillaries

remaining 80% (~480ml/min) of plasma flows through efferent arterioles to the peritubular capillaries

Question 30

The filtration of plasma per unit of time is known as the _________________. This is directly related to the perfusion pressure of the ________ capillaries which also means it is directly related to renal blood flow (RBF).

Answer 30

glomerular filtration rate (GFR)

glomerular

Question 31

Filtration fraction

Answer 31

ratio of glomerular filtrate to renal plasma flow per minute

125mL / 600mL = 0.20

Question 32

Normal urinary output (UO) in adults

Answer 32

~30ml/hour minimum (0.5-1 ml/kg/hr)

Question 33

Mechanisms of autoregulation of intrarenal blood flow (2)

Answer 33

1) Local autoregulation mechanism: mechanism to keep rate of glomerular perfusion (so GFR) constant over changes in arterial pressures/resistance. Purpose of autoregulation is to keep BRF and GFR constant when there are increases/decreases in systemic BP

2) Tubuloglomerular feedback: Purpose is to prevent large fluctuations in body water and salts. Macula dense cells in the distal tubule are able to sense increasing/decreasing amounts of filtered sodium, based on GFR increase/sdecreases in a nephron. When GFR and [Na+] increase, macula densa cells stimulate afferent arteriolar vasoconstriction and decrease GFR (and opposite occurs)

Question 34

What is the neural mechanism that regulates renal blood flow?

Answer 34

• Regulates water and sodium balance
• Kidney blood vessels are innervated by sympathetic nerve fibers (primarily on afferent arterioles)
• Decreased systemic BP = increased renal sympathetic nerve activity via reflex through carotid sinus and baroreceptors of aortic arch
• sympathetic nerves release catecholamines to cause vasoconstriction and:
  
  • Decreases RBF and GFR
  • Increases renal tubualr sodium and water reabsorption
  • increases BP
• Opposite effects with decreased sympathetic nerve activity
• Renalase - hormone released by kidney and heart that promotes metabolism of catecholamines to assist in BP regulation
• No significant parasympathetic regulation

Question 35

What is the hormonal mechanism of renal blood flow regulation?

Answer 35

• primarily through vasodilation/vasoconstriction

1) Renin-angiotensin-aldosterone system (RAAS) - can increase systemic arterial pressure and change RBF

• Renin formed and stored in juxtaglomerular apparatus, release triggered by decreased BP in the afferent arterioles, decreased [NaCl] in convoluted tubules, sympathetic nerve stimulation of β-adrenergic receptors on the juxtaglomerular cells, and the release of prostaglandins
• Results:
  
  • sodium reabsorption
  • systemic vasoconstriction
  • sympathetic nerve stimulation
  • thirst stimulation (increased fluid intake)

2) Natriuretic peptides: synthesized and released from the heart. Natural antagonists of RAAS. Cause vasodilation and increase sodium and water excretion and decrease BP. Assist in protecting the heart from volume overload.

• Urodilatin: renal natriuretic peptide made in cells of distal tubule and collecting duct; increase renal blood flow (causing diuresis)

Question 36

What are the functions of nephrons?

Answer 36

1) Filters plasma at glomerulus
2) Reabsorbs and secretes different substances along tubular structures
3) Forms a filtrate of protein-free fluid (ultrafiltration)
4) Regulates the filtrate to maintain body fluid volume, electrolyte composition, and pH within narrow limits

Question 37

Define the following terms.

Glomerular filtration

Tubular reabsorption

Tubular secretion

Excretion

Answer 37

Glomerular filtration: movement of fluid and solutes across the glomerular capillary membrane into the Bowman space

Tubular reabsorption: movement of fluids and solutes from tubular lumen to peritubular capillary

Tubular secretion: transfer of substances from th eplasma of peritubular capillary to tubular lumen (active and passive transport)

Excretion: elimination of a substance in the final urine

Question 38

Nephron function: Glomerular Filtration

What is it and what factors affect glomerular filtration?

Answer 38

What is it: fluid being filtered by the glomerular capillary filtration membrane that is then released into the PCT. Filtrate beomces protein free but has electrolytes (Na, Cl, K) and organic molecules (creatinine, urea, glucose) in the same concentrations as found in plasma

Factors affecting glomerular filtration:

• Permeability: Glomerulus is freely permeable to water, relatively impermeable to large colloids (like proteins). Small size of the filtration slits in glomerular epithelium also doesn’y allow big things crossing into the PCT.
• Capillary pressure: capillary hydrostatic pressure is the major force of moveing water and solutes across filtration membrane and into Bowman capsule. 2 forces oppose the filtration effects of glomerular capillary hydrostatic pressure:
  
  • 1) hydrostatic pressure in Bowman space (P_Bc)
  • 2) oncotic pressure of glomerular capillary blood

Question 39

What is net filtration pressure (NFP)? Describe which direction the NFP is favouring and how many mmHg of pressure is the NFP.

Answer 39

sum of forces favouring and opposing filtration

favours fluid movement from afferent arteriole into the Bowman space, NFP = 12mmHg

Question 40

Describe the movement of fluid between the afferent arterioles, Bowman capsule, and efferent arterioles based on their hydrostatic and oncotic pressures.

Answer 40

Pressures that favour filtration (into bowman capsule):

• Glomerular capillary hydrostatic pressure of afferent arteriole (47mmHg) and efferent arteriole (45mmHg)

Pressures opposing filtration (pushing/pulling fluid out of boman capsule):

• Bowman space hydrostatic pressure (10mmHg)
• Glomerular capillary oncotic pressure in afferent arteriole (25mmHg) and efferent arteriole (35 mmHg)

The low hydrostatic pressure and increased oncotic pressure in efferent arteriole then are transferred to peritubular capillaries and facilitate reabsorption at PCTs

Question 41

How much total volume of fluid is filtered by the glomeruli and how much of the filtrate is reabsorbed into the peritubular capillaries back to the blood?

Answer 41

Total average: 180L/day (or 120mL/min)

99% of filtrate reabsorbed (since we only excrete 1-2L of urine daily)

Question 42

What pathological conditions may cause an increase/decrease in GFR?

Answer 42

Increased GFR:

• obstruction to urine outflow - strictures, stones, tumors in that area will cause a retrograde increase in hydrostatic pressure at Bowman space which would decrease GFR (efferent arteriole pushing back)
• Low levels of plasma proteins in blood can cause decrease in glomerular capillary oncotic pressure leading to increased GFR

Decreased GFR:

• Excessive loss of protein-free fluid from vomiting, diarrhea, diuretics or sweating can increase glomerular capillary oncotic pressure and decrease GFR

Question 43

What is the main function of the proximal convoluted tubule (PCT)? What sorts of substances get reabsorbed/exchanged in this area of the nephron?

Answer 43

Function: A large amount of reabsorption occurs​. primarily active reabsorption of sodium with cotransport of water, most electrolytes, organic substances. Oncotic pressures also promote water reabsorption. This leads to increased [urea] within tubular lumen which creates a gradient for passive diffusion to the peritubular plasma.

Reabsorption:

• Na & H2O: 60-70%
• urea: 50%
• 90% of K, glucose, bicarbonate, Ca, phosphate, AA, uric acid
• all are passively absorbed via Na being the driving force (Cotransport)

Secretion:

• H+ ions: H+ exchanged with Na+ in tubular lumen, which than combines with HCO3- to make H2CO3. This then breaks down to CO2 and H2O and diffuse into tubular cell and then form HCO3- and H+ again. H+ secreted again and HCO3- combines with Na+ and transported to blood
• Organic bases and acids
• Creatinine
• Drugs/toxins

Question 44

What is transport maximum (T_m)?

Answer 44

phenomenon where some molecules’ active transport in the tubules rely on carrier molecules so what they’ve become saturated, they’ve reached their transport maximum (and the rest would have to be excreted in urine)

Question 45

What is glomerulotubular balance and how does it work?

Answer 45

The ability for the renal tubules (primarily proximal tubule) readjust and reasborb a constant proportion of the glomerular filtrate rather than a constant amount.

This works well because sometimes for whatever reason, the GFR may increase or decrease, so you want the tubules to be able to automatically adjust their rate of reabsorption of Na and H2O to balance out that change and prevent wide fluctuations in the xcretion of Na and water into the urine

Question 46

Urine concentration/dilution occurs primarily in what nephron structures?

Answer 46

Loop of Henle, distal tubules, & collecting ducts

the hairpin loop in the renal medulla allows kidney to concentrate urine and conserve water for body

Question 47

To produce concentrated urine involves a countercurrent exchange system. What is it and how does this system work?

Answer 47

Definition: Fluid exchange in opposite directions through parallel tubs of the loop of Henle, relying on concentration gradients.

Components:

• The longer the loop, the greater the concentration gradient (Gradient increases from cortex to tip of medulla)
• loops multiply the concentration gradient and vasa recta blood vessels act as a countercurrent exchanger for maintaining the gradient
• slow rate of blood flow also allows for the gradient to be preserved

How it works:

• 1) starts at thick ascending limb of loop of Henle, active Cl & Na transport out of tubular lumen and into medullar interstitium
• 2) ^ part of loop is impermeable to H2O so H2O cannot be reabsorbed with NaCl transport so fluid in tubule becomes hypoosmotic, medulla interstitium becomes hyperosmotic
• 3) descending limb of the loop (receives fluid from proximal tubule) is highly permeable to water but does not actively transport Na or Cl but may diffuse into descending tubule from interstitium so hyperosmotic interstitium causes H2O to move out of descending limb and whatever remains in the descending tubule becomes increasingly concentrated as it moves towards tip of medulla. In the descending limb of vasa recta, H2O moves out and Na/Cl in causing plasma to be increasingly concentrated as it flows towards tip.
• 4) Once fluid goes around the loop into ascending limb, Na and Cl are removed while water is retained. Fluid then becomes increasingly dilute as it encounters the distal tubule. In the vasa recta, surrounding interstitial fluid is relatively more dilute so H2O moves back into the blood vessel while Na and Cl diffuse out (plasma comes more filute)

Question 48

Uromodulin is produced in what structure and what is its function?

Answer 48

• aka Tamm-Horsfall protein (THP) & made in loop of Henle
• the most abundant protein in human urine
• bind to uropathogens to prevent UTIs, protect uroepithelium from injury, protects kidnet stone formation, associated with progression of kidney disease

Question 49

Describe what happens in the distal tubule and collectin duct (i.e. what gets excreted/reasborbed).

Answer 49

• Convoluted segment of distal tubule:
  
  • ​poor permeability to water
  • readily reabsorbs ions, contributes to tubular fluid dilution
• Straight segment and collecting duct:
  
  • permeable to water as controlled by ADH
  • sodium reabsorbed via aldosterone regulation
  • K actively secreted, also controlled by aldosterone
  • H+ secretion which combines with nonbicarbonate buffers (ammonium, phosphate) for acid elimination in urine (which contributes to acid-base balance)

Question 50

What is the composition of urine?

Answer 50

• clear yellow/amber colour
• Cloudiness - may be bacteria, cells, or high solute concentration present
• pH: 4.6-8.0 but normally acidic as protection from bacteria
• Specific gravity - 1.001-1.035
• Normal: does not have glucose, blood cells, occasionally traces of protein (with ++exercise)

Question 51

What hormones have an influence on nephron function?

Answer 51

1) ADH: controls final urine concentration. Secreted from posterior pituitary. Increases water permability and reabsorption in the last segment of the distal tubule and along collecting ducts (because urine is hypoosmotic in the ascending limb of loop of Henle). H2O diffuses into ascending limb of vasa recta and returns to circulation. Excreted urine now has high osmotic concentration.

2) Aldosterone: synthesized & secreted by adrenal cortex via RAAS. Stimulates epithelial cells of distal tubule and collecting duct to reabsorb Na (promoting water reabsorption) and increases K+ and H+ excretion

3) Natriuretic Peptides: specifically atrial natriuretic peptide (ANP) which are secreted from atria myocardial cells and brain natriuretic peptide (BNP) secreted from ventricular myocardial cells. During volume expansion/HF and heart dilates, ANP/BNP inhibit Na and water absorption by kidney tubules, inhibit secretion of renin and aldosterone, vasodilate afferent arterioles, constrict efferent arterioles. Result: increased urine formation to decrease blood volume & BP.

• Others: C-type natriuretic peptide - secreted from vascular endothelium, causes vasodilation in the nephron
• Urodilation: from distal tubules and collecting ducts, causes vasodilation and natriuretic and diuretic effects

Question 52

What is a diuretic and its function?

What are the 5 categoires of diuretics?

Answer 52

Definition: any agent that enhances urine flow

Function: interferes with renal Na reabsorption and reduces ECF volume. Vommon for HTN and edema 2’ HF, cirrhosis, nephrotic syndrome

Categories:

• 1) osmotic diuretics - acts in proximal tubule, attracts water and diminishes Na reabsorption
• 2) carbonic anhydrase inhibits - inhibits urinary acidification: acts in proximal tubule; inhibits CA, blocks H+ secretion and Na/HCO3- reabsorption
• 3) inhibitors of loop Na/Cl transport
• 4) aldosterone antagonists (potassium sparing) - acts on distal tubule/collecting ducts; blocks Na reabsorption but K is retained
• 5) aquaretics - acts on distal tubule/collecting ducts, blocks action of ADH

Question 53

What hormones are activated/synthesized by the kidney? (3)

Answer 53

1) Urodilatin

2) Vitamin D: hormone obtained from diet or synthesized by the action in UV rays on cholesterol in the skin. Initially inactive form vitamin D₃ (cholecalciferol) and requires two hydroxylations to become active. First step occurs in liver, second step in kidneys

3) Erythropoietin (Epo): stimulates RBC production in bone marrows in response to tissue hypoxia. Epo released when there is decreased O2 delivery to kidneys

Question 54

Formation steps and function of vitamin D

Answer 54

Function: necessary for absorption of calcium and phosphate by small intestine

Steps of Formation: renal hydroxylation step stimulated by PTH (and decreased plasma calcium levels stimulates PTH secretion) to restore [Ca2+]. Can also be influences by decreased levels of phosphate which would stimulate calcitrol formation

• 1. Calcium mobilization from bone
• 2. Synthesis of 1,25-dihydroxy-vitamin D3 (Calcitrol)
• 3. Absorption of calcium from the intestine
• 4. Increased renal calcium reabsorption
• 5. Decreased renal phosphate reabsorption

Question 55

What are renal clearance tests and why are they important?

Answer 55

determines hor much of a substance can be cleared from the blood by the kidneys per given unit of time

allows for an indirect measure of GFR, tubular secretion, tubular reabsorption, and renal blood flow

Question 56

How would you measure clearance and renal blood flow?

Answer 56

• with use of para-aminohippuric acid (PAH)
• some PAH is filtered at glomerulus and rest is secreted into tubules via kidney
  
  • If all PAH removed from plasma during a single pass through the kidney, total renal plasma flow (RPF) can be determined. But some of the supporting structures receive 10-15% of effective renal blood flow (ERBF) so….
  • clearance of PAH measures effective renal plasma flow (ERPF) which is 85-90% of true RPF

Question 57

How would you measure clearance and GFR?

Answer 57

• Measuring GFR best for knowing how functional your renal tissue is (assessed for kidney damage and drug dosing)
• Inulin would be ideal but instead we use creatinine clearance to measure GFR
  
  • creatinine freely filtered at glomerulus, but a littl ebit is secreted by renal tubules
• Cystatin C - stable protein in serum filtered at glomerulus and metabolized in tubules; often used to estimate GFR in mild/mod impaired renal function cases

Question 58

What can measuring the plasma creatinine concentration (P_cr) help you quantify?

Answer 58

• normal value: 0.7-1.2 mg/dl
• helpful in monitoring progressive changes in renal function (usually chronic diseases)
• usually has a stable value when GFR is stable because creatinine has a constant rate of production from muscle metabolism & amount filtered = amount excreted
• GFR has an inverse relationship with P_cr
  
  • so decreased GFR would have increased plasma creatinine accumulation
• P_cr can also increase with trauma and muscle tissue breakdown

Question 59

Why is measuring the concentration of urea nitrogen in the blood (BUN) important for renal function?

Answer 59

• BUN levels reflects glomerular filtration and urine-concentrating capacity
• Urea is filtered at the glomerulus so…..
  
  • increased BUN levels mean decrease in glomerular filtration
  • BUN increases in dehydration states & with acute/chronic renal failure

Question 60

What is urinalysis?

Answer 60

a cheap and noninvasive diagnostici procedure where they collect fresh urine & evaluate it for colour, turbidity (cloudiness), protein, pH, specific gravity, sediment, and supernatant (liquid above precipitant)

Question 61

How does renal function change in pediatrics?

Answer 61

• GFR only reaches adult levels at 1-2 y.o. (low birth weight infants have delay in achieving full renal function, may not have full GFR until 8 + greater risk of CKD once adults)
• newborns have decreased ability to efficiently remove excess water and solutes
• have shorter loops of Henle which means ability to concentrate urine also decreases (more dilute urine)
• Risks for metabolic acidosis while acid and base excreting mechanisms are still maturing meaning fluid and electrolyte balance can be easily upset
• Newborns diurese 2 to 3 days after birth

Question 62

How does renal function change with aging?

Answer 62

Structural changes:

• ↓ renal mass, tubules., ↑ # of sclerotic glomeruli
• interstitial fibrosis
• causes a slow decline in GFR and reduced creatinine clearance

Functional changes:

• less concentrating ability
• less able to tolerante dehydration, excessive water loads, electrolyte imbalances
• delayed response to acid-base changes and glucose reabsorption
• Drug eliminitation becomes shittier which may lead to toxic reactions
• Decreased thirst and diminished water intake
• hormones are wack

Other factors:

• Comorbidities like HTN and DM will accelerate renal function decline (obesity does not tho)

Question 63

What is the most common type of urinary dysfunction?

Answer 63

bladder infection

Question 64

Urinary Tract Obstruction

Answer 64

• interference with the flow of urine at any site along the urinary tract; obstruction can be anatomical or functional
• impedes flow & dilates structures proximal to blockage
• increases infection risk and renal function compromise

Question 65

Obstructive uropathy - What is it and what factors influence the severity of this?

Answer 65

Definition: anatomic changes in the urinary system caused by obstruction

Severity determined by:

• 1) location of obstructive lesion
• 2) involvement of ureters and kidneys
• 3) severity/completeness of the blockage
• 4) duration of blockage
• 5) nature of the obstructive lesion

Question 66

Upper Urinary Tract Obstruction

Common Causes & Pathophysiology

Answer 66

Common causes:

• stricture or congenital compression of a calyx at ureteropelvic-ureterovesical junction (stones/calculi or vesicoureteral reflux)
• compression from abnromal vessel, tumor, abdominal inflammation, scarry (retroperitoneal fibrosis)
• ureteral blockage from stones
• malignancy of renal pevis or ureter

Pathophysiology: causes dilation of ureter (hydroureter_)_, renal pelvis & calyces (hydronephrosis/ureterohydronephrosis), and renal parenchyma proximal to blockage site which backs up urine. Increased pressure transmitted to glomerulus which decreases filtration. Causes smooth muscle hypertrophy and urine accumulation and filation eventually leads to enlargement and tubulointersitital fibrosis with ++amounts of collagen and protein deposits.

• ^ happens within 7 days
• 14 days: adverse effects to distal and proximal tubules of nephron
• 28 days: damaged glomeruli and renal cortex; thinned medulla

Kidney unable to conserve Na, bicarb, water or excrete H or K which leads to metabolic acidosis and dehydration. Kidney may recover to partial function if blockage is removed within 56-69 days (4 month recovery) but typically complete obstruction causes irreversible damage within 4 weeks.

Question 67

Hydroureter

Answer 67

dilation of ureter (caused by accumulation of urine in ureter)

Question 68

Hydronephrosis/utereohydronephrosis

Answer 68

dilation of ureter and pelvicaliceal system

Question 69

What is compensatory hypertrophy/hyperfunction?

Answer 69

Definition: compensatory response from the body when there is unilateral obstruction. Results in two growth processes:

• 1) obligatory growth - via somatomedins
• 2) compensatory growth - via unknown source

Result: causes unobstructed kidney to increase the size of individual glomeruli and tubules. No change to total number of functioning nephrons. Reversible with relief of obstruction and recovery in the obstructed kidney

Question 70

What happens with relief of urinary tract obstruction?

What complications may there be?

Answer 70

• Postobstructive diuresis: brief period of diuresis; a physiological response that signals restoration of fluid and electrolyte imbalance caused by obstructive uropathy
• occasionally may cause rapid excretion of large volumes of H2O, Na, and other electrolytes (causing increased UO to 10L/day) but this may cause dehydration and more fluid/electrolyte imbalances so needs to be corrected
• Risk factors for severe postobstructive diuresis:
  
  • chronic bilateral obstruction
  • impairment of one/both kidneys’ ability to concentrate urine or reabsorb sodium (acquired nephrogenic diabetes insipidus)
  • HTN
  • edema & weight gain
  • CHF
  • uremic encephalopathy (brain dysfunction 2’ to toxin accumulation)

Question 71

Kidney Stones

Definition, Demographics

Answer 71

Definition: aka calculi/urinary stones - masses of crystals, proteins, other things that lead to urinary tract obstruction. Can be found in kidneys, ureters or bladder. Most are unilateral. Most common stone types: calcium oxalate/phosphate (70-80%), struvite (15%), uric acid (7%). Rare: cystine stones.

Demographics: recurrence rate ~30-50% within 5 years. Risk factors: age, sex, race, geographic location (indirectly affected by avg temperature, humidity, rainfall, which influences fluid intake and diety), seasonal factors, fluid intake, diet, and occupation. Most develop their first stone before 50 y.o. Reduced risk: in those that are active and drink loves of water.

Question 72

Kidney Stones

Pathophysiology (Stone formation & retention)

Answer 72

Stone formation related to:

• 1) supersaturation of 1+ salts in urine (more salts in the fluid than the volume is able to dissolve) - doesn’t have to be constant, even intermittently i.e. after meal ingestion, dehydration. diuretics
• 2) preciptation of salts from liquid to a solid state
• 3) growth through crystallization (from a small nidus to large stones) or agglomeration/aggregation - renal tubules and papillae also have surfaces that may attract a nidus and add matrix to it to form a stone
• 4) presence/absence of stone inhibitors - uromodulin, magnesium, potassium citrate, etc. inhibit crystal growth and reduce risk of stone formation

Other factors: temperature and pH of urine - alkaline urine pH ++risk of calcium phosphate stone formation. Acidic urine increases risk of uric acid stone formation

Retention/Excretion: Small stones (<5mm) 50-50 able to painfully pass through peeing, 100% no change if the stones at 1cm. Retention primarily occurs in papillary collecting ducts. Some conditions that cause urinary statis or anatomical abnormalities (i.e. BPH, strictures, inflammation within urintary tract) may increase risk of stones due to inability to flush crystals

Question 73

Types of kidney stones

Answer 73

1) Calcium stones: 70-80% of all stones requiring treatment (Calcium oxalate - 80%, calcium phosphate 15%). Most people have idiopathic calcium urolithiasis (ICU) (unknown etiology). Stones form in supersaturated urine or detach from interstitial sites within the tubules near tip of renal papillae. People at risk: hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia, mild renal tubular acidosis, crystal growth inhibitor deficiencies.

2) Struvite stones: magnesium-ammonium-phosphate + varying levels of matrix (matricx forms in alkaline urine or during bacterial infeciton). Large growths and branch into staghorn shapes

3) Uric acid stones: in those who excrete excessive uric acid in the urine (like those with gouty arthritis). Primarily a product of purines (so in those that eat a lot of meat and drink a lot of beer). Increased risk in consistently acidic urine for precipitation of cystine and xathine

Question 74

Kidney Stones

Clinical Manifestations, Diagnosis, Treatment

Answer 74

Clinical Manifesations: Renal colic (flank pain radiating to the groin) - usually indicative of osbtruction of renal pelvis or proximal ureter.

• Colic readiating to lateral flank or lower abdomen indicates obstruction in midureter
• lower tract sx (urgency, frequent voiding, urge incontinence) indicates obstruction of lower ureter or ureterovesical junction
• potentially N/V from pain & trace blood in urine

Diagnosis: based on Sx, hx taking, imaging studies, 24 hour urinalysis

Treatment: manage acute pain, promote stone passage, reduce size of current stones, and prevent new stone formation.

• 1) Manage pain
• 2) reduce concentration of stone-formaing substances via increasing urine flow rate with high fluid intake
• 3) adjusting urine pH
• 4) decreasing amount of stone forming substances in urine via diet changes, altering urine pH
• 5) percutaneous nephrolithotomy, ureteroscopy, ultrasonic/laser lithotripsi to remove stones and get them fragmented to be excreted
• Prevention: drink lots of water, diet changes (less animal protein, sodium, things with dietary oxalate in it; maintaining a reasonable calcium intake)

Question 75

What are Lower Urinary Tract Obstructive disorders?

What are the causes of obstruction and what is a common symptom?

Answer 75

• Disorders where there is obstruction of the lower urinary tract (LUT), primarily related to storage of urine in bladder or emptying of urine through bladder outlet
• Causes: neurogenic, anatomic alterations or both
• Common symptom: incontinence

Question 76

Types of incontinence

Answer 76

1) Urge incontinence: most common in elderly; involuntary loss of urine with abrupt and strong urge to void. Often associated with involuntary contractions of detrusor muscle (if neuro-related, then it’s destrusor hyperreflexia; if not neuro, then it’s detrusor instability & may be associated with decreased bladder wall compliance)

2) Stress incontinence: most common in women <60yo and men who’ve had prostate surgery. Involuntary loss of urine during coughing, sneezing, laughing, or other physical activity associated with increased abdominal pressure.

3) Overflow incontinence: Involuntary loss of urine with overdistention of bladder; associated with neurologic lesions below S1, polyneuropathies, and urethral obstruction (e.g., enlarged prostate)

4) Mixed incontinence: combo of stress x urge incontinence. Most common in older women.

5) Functional incontinence: involuntary loss of urine associated with dementia or immobility

Question 77

Neurogenic Bladder

Definition & Types of disorders

Answer 77

Definition: general term for bladder dysfunction due to neurologic disorders. Depends on where the lesions are in the NS.

Types:

• Dyssynergia - loss of coordinated neuromuscular contraction
• Lesions in sacral area of spinal cord/peripheral nerves - underactive, hypotonic or flaccid bladder function, often with loss of bladder sensation
• Detrusor hyperreflexia: overactive/unhibited or reflex bladder. UMN disorder causing bladder to empty automatically when full; external sphincter still intact
  
  • caused by neuro disorders above pontine micturition center (CVA, TBI, dementia, brain tumors)
• Detrusor hyperreflexia with vesicosphincter dyssynergia: Loss of pontine coordination of detrusor muscle contraction & external sphincter relaxation so bladder and sphincter contract at the same time. Minimal bladder relaxation during storage with small urine volumes and high bladder pressures = overactive bladder with frequent urge to void/urge incontinence, increased UTI risk.
  
  • _​_caused by lesion below pontine micturition center but above sacral micturition center (between C2-S1) (SCI, MS, Guillain-Barré syndrome, vertebral disk problems)
• Detrusor areflexia/acontractile detrusor: underactive bladder - acontractile/atonic bladder wtih urine retention and distenion. If bladder sensory innervation is still functionally, then full bladder will be sensed by muscle won’t contract leading to stress and overflow incontinence.
  
  • LMN disorder (lesions below S1 aka cauda equina syndrome) or peripheral nerve lesions (Myelodysplasia, MS, tabes dorsalis, peripheral polyneuropathies

Question 78

Overactive Bladder Syndrome (OAB)

Definition, Cause, Demographics/Risk factors, Clinical Manifestations

Answer 78

Definition: condition of detrusor overactivity resulting in involuntary detrusor contractions during bladder filling phase. Detrusor is too weak to empty the bladder which leads to urinary retention with overdlow/stress incontinence.

Cause: idiopathic

Demographics & Risk Factors: female, 65+. Risk factors: vaginal birth with forceps use, surgery for pelvic progan prolapse, decreased estrogen 2’ to menopause/hysterectomy, meds.

Clinical Manifestations: urinary urgency, frequency, nocturia with or without incontinence (and not caused by UTI or other known pathology)

Question 79

Types of anatomic obstructions to urine flow (5)

Answer 79

1) Urethral stricture: narrowing of urethral lumen; happens during infection/injury/surgery causes a scar that reduces the diameter. Mostly occurs in men, and severity is based on where the stricture is, length of it, and how much space is still left.

• More severe: if longer strictures, proximal > distal, size of blockage

2) Prostate enlargement: caused by acute inflammation, BPH, prostate cancer

3) Pelvic organ prolapse (in women): causes bladder outlet obstruction when cystocele (herniate of bladder into vagina) goes below level of urethral outlet.

4) Tumor compression

5) Partial obstruction of bladder outlet/urethra - initiall causes increase in force of detrusor contraction but persisting blockages will cause nerves to be damaged and result in urinary urgency/overactive bldder. Bladder wall eventually loses its ability to stretch and accommodate urine leading to low bladder wall compliance and eventually elevate pressures in system leading to impaired renal function

Question 80

Symptoms as a result of anatomic obstructions to urine flow

Answer 80

1) frequent daytime voiding (more than every 2 h while awake)
2) nocturia (waking up more than once/night to pee for those <65yo.; waking up 2+ times for 65+)
3) poor force of stream
4) intermittency with urinary stream
5) bothersome urinary urgency
6) feelings of incomplete bladder emptying despite peeing

Question 81

Evaluation and Treatment of Lower Urinary Tract obstructions

Answer 81

Diagnosis: Hx and physical exam, postvoid urine measurements (of bladder height and width), uroflowmetry (force of urinary stream). cystometric test (evaluates urine volume and pressure), functional imaging

Treatment:

• OAB and detrusor sphincter dyssynergia: a-adrenergic blocking (antimuscarinic) medications
• botulinum toxin A injections or surgery
• intermittent catheterization x anti muscarinics to prevent overactive bladder contractions
• Low bladder wall compliance: antimuscarinic drugs and intermittent catherization
• Prostate enlargement: treating underlying cause with meds and surgery, catheter
• Urethral stricture: urethral dilation
• Strictures: surgery

Question 82

Renal Tumors

Description (Types, Risk Factors), Pathophysiology, Clinical Manifestations, Diagnosis, Treatment

Answer 82

Types:

• Renal adenomas (benign): uncommon; encapsulated tumors that are located near cortex of kidney. Can become malignant so need to be removed
• Renal cell adenocarcinoma (RCC): the most common renal neoplasma
• Renal transitional cell carcinoma (RTCC): rare, arises in renal parenchyma and renal pelvis. More common in men

Risk factors: smoking, obesity, uncontrolled HTN

Pathophysiology: RCCs usually arise from tubular epithelium in renal cortex. Unknown etiology. Classified based on cell type and extent of metastasis (clear cell tumors the most common). Tumors usually occur unilaterally.

Clinical Manifestations: **hematuria, dull aching flank pain, palpable flank mass, weight loss** (classic signs but represent advantaged disease stage).

• Painless hematuria (early stages)
• Common sites of distant metastasis: lungs, lymph nodes, liver, bone, thyroid gland, CNS

Diagnosis: Clinical Sx, X-ray of abdomen, various tests. Use of TNM classification to stage RCC

Treatment: surgical removement of affected kidney or partial nephrectomy if smaller tumors. Chemo drugs. Immuotherapy if metastasis.

Question 83

Bladder Tumors

Description, Pathogenesis, Clinical Manifestations, Diagnosis, Treatment

Answer 83

Description: 5th most common malignancy. Most common in 60+ y.o. men. Most common bladder malignancy is transitional cell (urothelial) carcinoma

Pathogenesis: Risk is greatest among those who smoke, heavily exposed to metabolites of aniline dyes, ++arsenic levels in drinking H2O, heavy consumption of phenacetin, or infection. Bladde cancer results from genetic alteration in normal bladder epithelium. Metasis usually to lymph nodes, liver, bones, lungs.

Clinical Manifesations: **gross painless hematuria** with recurrent episodes and accompanied by bothersome LUT symptoms (daytime voiding frequency, nocturia, urgency, urge incontinence). Potential flank pain.

Evaluation/Diagnosis: tissue biopsy, urine cytologic study

Treatment: laser ablation or transurethral resection + chemo therapy

Question 84

What is a urinary tract infection (UTI)? Who is at risk of developing UTIs?

Answer 84

Description: inflammation of the urinary epithelium usually caued by bacteria from gut flora. Can occur anywhere along urinary tract (urethra, prostate, bladder, ureter, kidney). UTI occurs when a pathogen circumvents or overwhelms the hosts defences mechanisms and rapidly reproduces.

Risk factors: preemies, prepuberties, sexually active and preggo women, women with antibiotics that have disrupted vaginal flora, spermicide users, estrogen-deficient postmenopausal women, those with indwelling cathters, ppl with DM, neurogenic bladder, UT obstruction.

Question 85

Uncomplicated vs complicated UTI

Answer 85

Uncomplicated UTI: infections that are mild and without complications, occur in those with a normal urinary tract

Complicated UTI: when there is an abnormality in urinary system or health problem compromising host defences (ex. HIV, renal transplant, diabetes, SCI)

Question 86

What factors in the body normally help to protect a person against UTIs?

Answer 86

• bacteria washed out of the urethra with micturition
• low pH, high osmalilty of urea, uromodulin, secretions from uroepithelium = bactericide
• utereovesical junction closes during bladder contraction to preven treflex of urine to ureters/kidneys
• Longer urethras and present of prostatic secretions in men also decrease risk of infection

Question 87

Types of UTI

Answer 87

Acute cystitis

Painful Bladder syndrome/Interstitial Cystitis

Acute Pyelonephritis

Chronic Pyelonephritis

Question 88

Most common and 2nd most common pathogens of UTIs

Answer 88

Most common: E. coli

2nd most commo: Staphylococcus saprophyticus

Question 89

Acute Cystitis

Definition, Types, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment

Answer 89

Definition: inflammation of the bladder, the most common site of UTI

• Mild cystitis: red inflamed mucosa
• Hemorrhagic cystitis: more advanced UTI with diffuse hemorrhage
• Supparative cystitis: UTI with pus and suppurative exudates on epithelial surface of the bladder
• Ulcerative cystitis: ulcers form from prolonged infection & sloughing of bladder mucosa
• Gangrenous cystitis: most severe infections leading to necrosis of bladder wall

Pathophysiolgy: most common infecting microorganisms: E.coli; 2nd most common: Staph. saprophyticus. Others: fungi, viruses, parasites, tubercular bacilli. Schistosomiasis - most common cause of parasitic invasion of the urinary tract globally.

• Bacteria (gram-ve bacilli) contaminates by moving retrograde into urethra and bladder, then ureter and kidney
• Bacteria bind to receptors on uroepithelium and resist flushing during peeing
• Infection triggers inflammatory resopnse causing edema in bladder wall and stimulating discharge of stretch receptors = symptoms of bladder fullness with small urine volumes, urgency and frequent urination
• Blood infections are uncommon & often preceded by septicemia

Clinical Manifesations: frequency, urgency, dysuria (painful urination), suprapubic and low back pain. Hematuria, cloudy urine, and flank pain more serious. Elderly with cystitis may be asymptomatic or demonstrate confusion or vague abdo discomfort. Reccurent UTIs and other concurrent illness have a higher risk of mortality. May be asymptomatic but still requires tx if cultures are +ve.

Diagnosis: urine culture of specific microorganism (10 000/ml or more) in freshly voided urine. Urine dipstick +ve for leukocyte esterase/nitrite reductase.

Treatment: antibiotics (3-7 days). Complicated UTI requires 7-14 days, potential for relapsing infection within 7-10 days. Follow up urine cultures should be obtained.

• Increased fluid intake
• Avoidance of bladder irritants
• Urinary analgesics

Question 90

Painful Bladder Syndrome/Interstitial Cystitis (PBS/IC)

Definition, Demographics, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment

Answer 90

Definition: unpleasant sensation (pain, pressure, discomfort) related to bladder and LUT symptoms for 6+ weeks without infection or other causes. Condition that includes

• nonbacterial infectious cystitis (viral, mycobacterial, chlamydial, fungal)
• noninfectious cystitis (radiation, chemical, autoimmune, hypersensitivity) - most common in immunocompromised; associated with radiation/chemo for pelvic & urogenital cancers
• interstitial cystitis

Demographics: most common in women 20-30 w/ Sx of cystitis (frequency, uregency, dysuria, nocturia) but -ve urine cultures and no other known cause.

Pathophysiology: unknown cause. Potential autoimmune reaction (mast cell activation, altered cell permeability, increased sensory nerve sensivity). Bladder fibrosis may occur with hemorrhagic ulders leader to decreased bladder volume. Uroepithelial layer also becomes more susceptible to bacterial penetration.

S/s: bladder fullness, urinary frequency (including nocturia), small urine volume, and chronic pelvic pain with symptoms lasting longer than 9 months

Diagnosis: rule out other diagnoses & extensive evaluation

Treatment: No single tx is effect. Oral & intravesicle therapys, sacral nerve stim., botox for Sx relief. surgery

Question 91

Acute Pyelonephritis

Definition, Common causes, Risk factors, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment

Answer 91

Definition: infection of one/both upper urinary tracts (ureter, renal pelvix, interstitium)

Common causes: ​

• Kidney stones: obstructing urine leads ot bacteriuria and hydronephrosis (kidney swelling) & traps bacteria causing irritation of epithelial lining
• Vesicoureteral reflux: chronic urine reflux up ureter into kidney during peeing leads to bacteria infection
• Pregnancy: Dilation and relaxation of ureter with hydroureter and hydronephrosis, due to obstruction from enlarged uterus and urethral relaxation caused by higher progesterone levels
• Neurogenic bladder: neuro impairment of normal bladder contraction with residual urine and ascending infection
• Instrumentation: introduces organisms into urethra and bladders (catheters); urinary tract (endoscopes)
• Female sexual trauma: organis move from urethra into bladder with infection, and spread up to kidney

Risk factors: most common - **urinary obstruction and urine reflux from bladder**. May be one or both kidneys. Most cases in women.

Pathophysiology: E. coli, Proteus, or Pseudomonas (last two more commong from instrumentation or urinary tract surgery. Microoganisms turn urea into ammonia which makes alkaline urine increasing risk of stone formation. Infection spreads along ureters and eventually may occur its way into bloodstream. Inflammation affecting pelvix, calcyces, and medulla and causes WBC infiltration with renal inflammation, edema, purulent urine. If severe, may lead to local abscesses in the medulla and extend into cortex. Tubules primarily affected. Necrosis of renal papillae can occur. Healing occurs after acute phase with fibrosis and atrophy of affected tubules. Rarely causes renal failure.

Clinical Manifestations: acute - fever chills, flank/groin pain. Characteristics of UTI (frequency, dysuria, costovertebral tenderness) may precede systemic S/S. Older adults - nonspecific (low grade fever and malaise).

Diagnosis: urine culture, urinalysis, and S/S (to differentiate from cystitis)

Treatment: Uncomplicated - 2-3 weeks of antibiotic therapy and follow up urine cultures. Antibiotic resistant microorganisms of re-infection may occur if there is urinary tract obstruction or reflex. Potential need for surgical corrections

Question 92

Chronic Pyelonephritis

Answer 92

Definition: presistent/recurrent infection of the kidney leading to scarring of one or both kidneys. Possibly due to recurrent infections from acute pyelonephritis but hard to determine.

Risk factors: in those who have renal infections associated with some type of obstructive pathological conditions (renal stones, vesicoureteral reflux)

Pathophysiology: Chronic urinary tract obstruction prevents elimination of bacteria, starting a process of progressive inflammation, alterations of renal pelvis and calyces, tubule destruction, atrophy or dilation and diffuse scarring. Impaired urine-concentrating ability leading to chronic kidney failure. Lesions are called “chronic interstitial nephritis”

Clinical Manifestations: early: minimal sx *HTN, frequency, dysuria, flank pain). Progresses to kidney failure (esp in the presence of obstructive uropathy or DM)

Diagnosis: urinalysis, IV pyelography, ultrasound

Treatment: treat underlying cause. Relieve obstruction and potential antibiotics

Question 93

Acute Glomerulonephritis

Definition, Causes, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment

Answer 93

Definition: inflammation of the glomerulus

• caused by primary glomerular injury (immunologic responses, ischemia, free radicals, drugs, toxins, vascular disorders, infection).
• Secondary glomerular injury: caused by systemic diseases (DM, HTN, bacterial toxins, SLE, CHF, HIV related kidney disease)

Causes: Immune mechanisms a major cause of injury. Injury damages glomerular capillary filtration membrane. Most commong types of immune injury:

1. deposits of antigen-antibody immune complexes in glomerule (type III hypersensitivity)
2. reaction of antibodies in situ against planted antigens within the glomerulus (type II hypersensitivity)

• Nonimmune glomerular injury due to: ischemia, metabolic disorders, toxin exposures, drugs, vascular disorders, and infection with direct glomerular cell injury

Pathophysiology: Inflammation triggers immune injury (which occurs after antigen-antibody deposits) where complement, neutrophils, monocytes, and T lymphocytes get attracted to that area. This injures the filtration membrane and increases permeability while reducing SA. GFR decreases leading to increased creatinine levels. Swelling and proliferation of cells and Bowman space lead to crescent moon shape). The result is decreased glomerular blood flow, decreased driving hydrostatic pressure, decreased GFR, and hypoxic injury

• Protein and RBCs also moves into urine (proteinuria or hematuria)
• Glomerular damage - depends on size, number, location of cells injured, exposure dureaction and type of antigen-antibody complexes

Clinical Manifestations: suddent or insidious onset. Silent, mild, mod, or severe Sx

• ++loss of nephron function until symptoms occur
• Focal lesions: less severe; edema, HTN
• Severe/progressive: Oliguria (low urine output), HTN, renal failure. Two major symptoms:
  
  • 1) hematuria with red blood cell casts
  • 2) proteinuria >3-5g/day with albumin being the major protein

Diagnosis: progressive development of clinical manifestations and lab findings of abnornaml urinalysis (proteinuria, RBCs, WBCs, casts). Other tests to look at antigen-antibody complex patterns. Reduced GFR, increased urea/creatinine etc.

Treatment: treat primary disease, preventing/minimizing immune responses, correcting other problems (edema, HTN, hypoalbuminemia, hyperlipidemia).

• diuretics and dialysis - for edema
• antibiotics for infection
• corticosteroids to suppress inflammatory responses (or cytotoxic agents if not responsive to corticosteroids
• Anticoagulants to control fibrin crescent formation

Question 94

Types of Glomerulonephritis

Answer 94

• depends on cause, pathological lesions, disease progression (acute, rapidly progressive, chronic) or clinical presentation (nephrotic syndrome, nephritic syndrome, acute/chronic renal failure)
• In almost all types: epithelial or podocyte layer of the glomerular capillary membrane is disturbed with loss of negative charges and changes in membrane permeability, expanded matrix and thickened basement membrane
• 1) Acute post-infectious related glomerulonephritis: results from untreated infection in skin/throat; immune complexes deposite in glomerulus. Decreased capillary blood flow and GFR
• 2) Crescentic/rapidly progressive glomerulonephritis: antibodies/immune complexes deposit in situ. Leads to crescent shaped lesions. Renal failure can occur within 3 mos
• 3) Mesangial proliferative glomerulonephritis: abnormal IgA bind and cause proliferation of mesangium in glomerulus
• 4) Minimal change disease: ++protein loss in urine, no immune depositys
• 5) ​Focal segmented glomerulosclerosis: similar to ^
• 6) Membranous nephropathy: antibodies cause thickening of glomerular capillary wall leading to damage
• 7) Membranoproliferative glomerulonephritis: thickening of basement membrane and mesangial cell proliferation
• 8) IgA nephropathy (Berger Disease): elevated IgA levels deposit and cause sclerosis and fibrosis of glomerulus & crescent formation
• 9) Chronic glomerulonephritis: can be due to any glomerulonephritis that eventually leads to end stage kdiney disease

Question 95

What is diabetic nephropathy and what complications can arise?

Answer 95

Definition: deterioration in kidney function 2’ to diabetes. Poorly controlled diabetes can cause damage to blood vessel clusters in your kidneys that filter waste from your blood.

• Most common cause of CKD and end-stage renal failure

Complications:

• progressive thickening and fibrosis of glomerular basement membrane
• nodular expansion of mesangial matrix with albuminuria, popcyte loss, tubular epithelial cell atrophy, progression to chronic renal failure

Question 96

What is lupus nephritis and what complications can arise?

Answer 96

Definition: complication of lupus. Caused by autoantibodies forming against DNA with glomerular deposition of immune compelxes and alterations in B and T cells.

Complications: Complement activation and inflammatory events - damages glomerular membrane with mesangial expansion

Question 97

Chronic Glomerulonephritis

Answer 97

Definition: general term for several glomerular diseases that progress towards chronic kidney failure. May be no history of kidney disease before dx

Pathophysiology: associated with hypercholesterolemia and proteinuria. Potential mechanism is related to hyperfiltration and inflammatory processes. Renal insufficiency kicks in 10-20 years later, followed by nephrotic syndrome and fast progression to end-stage renal failure with potential need for dialysis or kidney transplant

Question 98

Nephrotic vs nephritic syndrome

Answer 98

Nephrotic syndrome: excess amount of protein in the urine (3.5+ grams/day)

• happens when filtration of proteins > tubular reabsoprtion
• Causes:
  
  • primary forms - *minimal change nephropathy* (lipoid nephrosis), membraneous glomerulonephritis, focal segmental glomerulosclerosis
  • secondary forms: systemic diseases like DM, amyloidosis, SLE
  • drugs (NSAIDS), infections, malignancies, vascular disorders
• more common in children than adults

Nephritic syndrome: an excess amount of blood in the urine. Usually less severe than in nephrotic syndrome. Occurs primarily with infections

Question 99

Nephrotic Syndrome

Pathophysiology, Clinical Manifestations, Dx, Treatment

Answer 99

Pathophysiology: basement membrane disrupted and podocyte injury = increased permeability to protein and loss of electrical -ve charge. Start to lose plasma proteins (albumin the most and then some immunoglobulins), decreases plasma oncotic pressure and results in edema. Loss of albumin stimulates lipoprotein synhesis by the liver and hyperlipidemia, promoting progression of glomerular disease. Loss of Ig may increase susceptibility of inections. Sodium retention common.

Clinical Manifestations:

• ++proteinuria: due to increased glomerular permeability and decreased reabsorption
• Hypoalbuminemia: lost in urine
• Edema: low levels of albumin and minimal to ANPs (pitting generalized edema)
• Hyperlipidemia: increased synthesis of lipoproteins (increased cholesterol, triglycerides, phospholipids)
• Lipiduria: sloughing of tubular cells with fat in them leading to fat droplets in urine
• Vitamin D deficiency: due to loss of transport proteins and decreased vit D activation by kidney
• Hypothyroidism: from urinary loss of thyroid-binding protein and thyroxine

Diagnosis: when protein level in 24 hr urine collection >3.5g. Decreased serum albumin, increased cholesterol, phospholipids, triglycerides and potential fat bodies in urine.

Treatment: diet - moderate protein restriction, low fat and salt. Diuretics for fluid and HTN. Heparinoids for anticoagulation. Glucocorticoids to control immune disease. ACE inibitors/ARBs to lower urine protein excretion

Question 100

Nephritic Syndrome

Pathophysiology, Clinical Manifestations, Dx, Treatment

Answer 100

Pathophysiology: microscopic hematuria with RBC casts + proteinuria (not severe). Caused by increased permeability of glomerular filtration membrane with pore sizes that are big and allow RBCs and protein to get through

• associated with ostinfectious glomerulonephritis, rapidly progressive (crescentic) glomerulonephritis, IgA nephropathy, lupus nephritis, and diabetic nephropathy
• related to immune injury of the glomerulus
• HTN and uremia occur in advanced stages of disease.

Clinical manifestations: as above^ blood and protein in urine

Diagnosis/Tx: similar to nephrotic syndrome. Tx is high dose corticosteroids and potentially plasma exchange

Question 101

Define the following terms that describe kidney dysfunction.

Renal insufficiency

Renal failure

End-stage kidney disease

Answer 101

Renal insufficiency: renal function declines to ~25% of normal(GFR of 25-30 ml/min). Mild elevations of serum creatinine and urea

Renal failure: significant loss of renal function

End-stage kidney disease (ESKD): when <10% of renal function remains

Question 102

Uremia (Uremic syndrome)

Answer 102

• syndrome of renal failure, includes elevated blood urea and creatinine levels & fatigue, anorexia, N/V, pruritus, and neurologic changes
• Represents results of renal failure (retention of toxic wastes, deficiency states, electrolyte disorders, and immune activation promoting a proinflammatory state)

Question 103

Azotemia

Answer 103

• characterized by increased BUN levels (normal: 8 to 20 mg/dl) and frequently increased serum creatinine levels (normal: 0.7 to 1.4 mg/dl)
• caused by renal insufficiency or renal failure causes azotemia

Question 104

Acute Kidney Injury (AKI)

Definition, Pathophysiology (include types of AKI)

Answer 104

Definition: sudden decline in kidney function with decreased glomerular filtration and urine output, accumulation of nitrogenous waste products in blood (increased creatinine and BUN levels)

• Classified as RIFLE: Risk, Injury, Failure, Loss, ESKD

Pathophysiology: results from ischemic injury related to extracellular volume depletion and decreased renal blood flow, toxic injury from chemicals, or sepsis-induced injury. Inflammatory response, vascular response, and cell death occurs. Can be classified as:

• Prerenal (inadequate kidney perfusion) - the most common reason for AKI
  
  • hypovolemia (hemorrhaging, loss of plasma volume, burns, water and electrolyte losses)
  • hypotension or hypoperfusion - shock, decreased CO, massive PE, stenosis or renal vasoconstriction
  • leads to ischemicell injury and acute tubular necrosis if blood flow not restored
• Intrarenal (involve renal parenchymal/interstitial tissue)
  
  • Acute tubular necrosis (ATN), nephrotoxic ATN from radiocontrast media, acute glomerulonephritis, vascular disease, allograft rejection, interstitial disease
  • ATN commonly from with ischemia post-op lead to inflammatory response and then free radicals that injure cells
• Postrenal (urinary tract obstructive disorders) - obstructive uropathies (nuerogenic bladder, ureteral destruction, badder neck obstruction)
  
  • rare
  • several hours of anuria with flank pain followed by polyuria is a characteristic finding
  • obstruction causes increased intraluminal pressure upstream from obstruction site with gradual GFR decrease

Question 105

Oliguria (low urine output) can occur with AKI. What are the three mechanisms that cause this decrease in urine output?

Answer 105

1) Alterations in renal blood flow: Release of angiotensin II causes efferent arteriolar vasoconstriction or there may be redistribution of blood flow from the cortex to the medulla. Autoregulation of blood flow may be impaired, resulting in decreased GFR. Changes in glomerular permeability and decreased GFR also may result from ischemia.

2) Tubular obstruction: Necrosis of the tubules causes sloughing of cells, cast formation, or ischemic edema that results in tubular obstruction. Causes a retrograde increase in pressure and reduces the GFR. Renal failure can occur within 24 hours.

3) Tubular backleak: Normal glomerular filtration but tubular reabsorption of filtrate is accelerated due to permeability caused by ischemia an dincreased tubular pressure from obstruction

Question 106

Clinical Manifestations of AKI

Answer 106

3 overlapping phases:

1) Initiation phase - phase of reduced perfusion or toxicity. Kidney injury is evolving. Prevention of injury is possible during this phase

2) Maintenance/oliguric phase - period of established kidney injury and dysfunction after the initiating event has been resolved, may last from weeks to months. Urine output is lowest during this phase and serum creatinine and blood urea nitrogen (BUN) levels both increase

3) Recovery/polyuric phase - when glomerular function returns but the regenerating tubules cannot concentrate the filtrate. Diuresis is common during this phase, with a decline in serum creatinine and urea concentrations and an increase in creatinine clearance.

Other manifestations: non-oliguric renal failure (potentially), hyperkalemia, hyperphosphatemia, and metabolic acidosis from decreased urine excretion. Edema and CHF due to fluid retention. Potential fluid electrolyte balance issues with changes in urine volume throughout the phases

Question 107

Diagnosis and Treatment of AKI

Answer 107

Diagnosis: Depends on the cause - hx taking, urinalysis, measuring plasma creatinine and BUN levels

Treatment: PREVENTION - avoiding hypotension, hypovolemia, nephrotoxicity

• 1) correcting fluid electrolyte disturbances, particularly hyperkalemia;
• 2) managing BP
• (3) preventing and treating infections;
• (4) maintaining nutrition;
• (5) monitoring drug and metabolic excretions and whether they’re building up to toxic levels in the body

Question 108

What is chronic kidney disease (CKD) and what are common causes/risk factors?

Answer 108

Definition: progressive loss of renal function associated with systemic diseases & affects nearly ALL organ systems. Can progress from AKI

• National Kidney Foundation defines kidney damage as a GFR <60 ml/min/1.73 m² for 3 months or more, irrespective of cause.

Causes:

• Systemic diseases - DM (most significant risk factor), HTN, SLE
• Intrinsic Kidney diseases - AKI, chronic glomerulonephritis, chronic pyelonephritis, obstructive uropathies, or vascular disorders

Question 109

What are the stages of CKD?

Answer 109

Stage I: normal kidney function (GFR >90ml/min). S/S: HTN but usually nothing else.

Stage II: mild kidney damage, mild reduction in GFR (60-89ml/min). S/S: HTN, increasing creatinine and urea levels)

Stage III: mod kidney damage (GFR 30-59 ml/min). S/S: mild, similar to Stage II

Stage IV: severe kidney damage (GFR 15-29 ml/min). S/S: as above & EPO deficiency anemia, hyperphosphatemia, increased triglycerides, metabolic acidosis, hyperkalemia, salt/water retention

Stage V: ESKD, established kidney failure (GFR<15 ml/min). Severe S/S ^

Question 110

What’s happening pathophysiologically in CKD?

Answer 110

• many things. A lot of it is driven by increased creatinine, urea, and K levels. Salt water balance also starts to go once the kidneys are too tired to continue compensating
• Intact nepphron hypothesis: basically says that kidneys are able to adapt when there is loss of nephron mass by hyperstrophy and hyperfunction of the other remaining nephrons (allow the kidneys to maintain normal function while GFR starts to decline)
• Progressive sclerosis and fibrosis occurs
• Two factors that advanced renal disease:
  
  • Proteinuria: contributes to tubulointerstitial injury by accumulating in interstitial space of nephron tubules. Also activates complement proteins and other shit that promotes inflammation and progressive fibrosis
  • Angiotensin II: promotes glomerular HTN and hyperfiltration caused by efferent arteriolar vasoconstriction. Constant high pressure causes increased glomerular capillary permeability which then causes proteinuria. May also promote inflammatory cell and growth factor activity that’s part of the fibrosis and scarring problem

Question 111

CKD causes MANY systemic effects seen in its clinical manifestation. How does it affect creatinine and urea clearance?

Answer 111

as GFR declines, plasma creatinine levels increases. So does plasma urea concentration

Question 112

How does CKD affect fluid and electrolye balance, and how does that manifest via signs and symptoms?

Answer 112

• When GFR drops to 25% function, s_odium (and thus water) becomes lost_ as an adaptive mechanism and requires diet intake to keep up to prevent sodium deficits and volume depletion
• Continued decline of GFR causes loss of tubular function to dilute/concentration urine (so urine specific gravity becomes fixed, this is how dense your urine is)
• Eventually kidney loses ability to regulate sodium and water balance, they become retained and then cause edema, proteinuria, HTN
• In early kidney failure: K retained while lots more gets lost through the bum. Once oliguria sets in, [K] increases to life-threatening levels requiring dialysis
• Metabolic acidosis: due to decreased H+ elimination and HCO3- reabsorption (when GFR <25-25%)

Question 113

In a CKD patient, what calcium, phosphate, and bone-related changes occur?

Answer 113

• bone and skeletal changes start when GFR <25%
• Hypocalcemia is accelerated by impaired renal synthesis of calcitriol or 1,25-dihydroxy-vitamin D3 (active form of vitamin D) with decreased intestinal absoprtion of calcium; also decreased renal phosphate excretion causes the phosphate to bind to calcium and further exacerbate the low calcium
• Decreased serum calcium level stimulates PTH secretion with mobilization of calcium from bone
• Leads to increased risk for fractures and osteoporosis, osteomalacia, osteitis fibrosa

Question 114

How is protein, carbohydrate, and fat metabolism changed in CKD?

Answer 114

• Proteinuria, metabolic acidosis, inflammation, and a catabolic state (all lead to -ve nitrogen balance)
• Protein levels diminish and loss of muscle mass occurs
• Insulin resistance and glucose intolerance
• DLD -lead to accelerated atherosclerosis and vascular calcification

Question 115

Clinical manifestations in a CKD patient regarding the cardiovascular system

Answer 115

• HTN due to excess sodium (and thus water) and fluid volume and arteriosclerosis
• Endothelial cell dysfunction and calcium deposits cause loss of vessel elasticity and vascular calcification
• Elevated [renin] also stimulates secretion of aldosterone which increases sodium reabsorption
• DLD promotes plaque formation
• increases the risk for ischemic heart disease, CVA, CHF (fluid overload), PVD
• Decreased EPO production causes anemia causing increased demands for cardiac output and workload (uremia also decreases RBC lifespan)
• Uremic toxins cause pericarditis
  *

Question 116

What changes occur in a CKD patient’s respiratory system?

Answer 116

• fluid overload, CHF, dyspnea
• pulmonary edema develops
• metabolic acidosis causing Kussmaul respirations
• pulmonary HTN due to LV dysfunction or uremic-associated vascular changes

Question 117

What hematological alterations occur in a CKD patient?

Answer 117

• normochromic-normocytic anemia
• impaired platelet function
• hypercoagulability
• Inadequate production of erythropoietin decreases red blood cell production and uremia decreases red blood cell life span
• lethargy, dizziness, low Hct
• Defects in platelet aggregation leading to increased bleeding tendency, bruises, epistaxis, GI bleeds, cerebrovascular hemorrhaging

Question 118

What immune system alterations occur in a CKD patient?

Answer 118

• Dysregulated immune system
• Suppressed chemotaxis, phagocytosis, antibody production, and cell-mediated immune response
• Systemic inflammation
• increased risk for infection

Question 119

What neurological alterations occur in a CKD patient?

Answer 119

• headache, pain, drowsiness, sleep disorders, impaired concentration, memory loss, and impaired judgment (known as uremic encephalopathy)
• Advanced stages of renal failure: may progress to seizures, coma
• Neuromuscular irritation can cause hiccups, muscle cramps, muscle twitching
• Peripheral neuropathies associated with uremic toxins also can develop with impaired sensations, particularly in LE
• Symptoms improve with hemodialysis

Question 120

What GI alterations occur in a CKD patient?

Answer 120

• bleeding ulcer and ++ blood loss
• anorexia, N/V/D, constipation
• Uremic fetor (bad breath caused by urea breakdown by salivary enzymes)
• malnutrition

Question 121

Changes to endocrine and reproductive systems in a CKD patient

Answer 121

Reproductive:

• decreased circulating sex steroids
• Males: reduced testosterone levels, may be impotent & infertility
• Females: reduced estrogen levels, amenorrhea, difficulty maintaining pregnancy to term
• Decreased libido and fertility in both genders

Endocrine system:

• insulin resistance common with uremia - CKD progression causes kidney’s ability to degrade insulin to be reduced leading to longer half life (so careful management is required)
• hypothyroidism - uremia delays response of TSH receptors

Question 122

What changes to the integumentary system occur in a CKD patient?

Answer 122

• anemia causing pallor and bleeding into the skin resulting in hematomas and ecchymosis
• Sallow skin colour - due to retained urochromes (yellow pigment)
• Uremic frost (uremic skin residues) and hyperparathyroidism associated with inflammation, irritaiton, and pruritius with scratching, skin picking, increased infection risk
• Half-and-half nails (half white and half red/brown)
  *

Question 123

Chronic Kidney Disease

Evaluation, Treatment

Answer 123

Diagnosis: early screening - risk factors, history, S/S, diagnostics (creatinine and urea levels elevated). Ultrasound, CT, X-ray to show small kidney size. Renal biopsies

Treatment:

• management via dietary restriction of protein, sodium, potassium, phosphate, vit D supplementations
• ACE inhibitors or ARBs for HTN, reduce proteinuria, prevent progressive renal damage
• glycemic control
• End-stage renal failure: conservative care, continuous renal replacement therapy, supportive therapy, renal transplantation

Question 124

Horshoe kidney

Answer 124

Definition: fused kidneys causing single U-shaped one

Clinical Manifestations: 1/3 are asymptomatic. Others: hydronephrosis (kidney swelling), infection, stone formation, renal malignancies (rare)

Question 125

Hypospadias

Definition, Causes, Clinical Manifestations, Treatment

Answer 125

Definition: congenital condition where urethral meatus is located on the ventral side/undersurface of penis (can be anywhere on the glands, penile shaft, base of penis, penoscrotal junction or perineum). most common anomaly of the penis.

Cause: genetic x endocrine x environmental. Advanced maternal age and low birth weight potentially contribute to it.

Clinical Manifestations:

• Chordee: penile torsion may occur - skin tethering and shortening of subQ tissue will cause the penis to bend or “bow ventrally”; penil shaft rotated
• Partial absence of foreskin and undescended testes (cryptochidism)

Treatment: corrective surgery - straight penis to allow sex as a adult, uniform urethra to allow urination without spraying all over the place, cosmetics. Usually done between 6-12 mos.

Question 126

Epispadias

Definition, Clinical Manifestations, Treatment

Answer 126

Definition: congenital defect where urethra doesn’t form in the normal location. It’s the same as exstrophy of the bladder (same defect) but just expressed to a differing degree.

• Males: urethral opening on dorsal surface of penis; predominantly in males
• Females: cleft aong urethra extends to bladder neck

Clinical Manifestations: small urethral opening that’s behind the glans (anterior epispadias) or a fissure may extend the length of the penis & into the bladder neck (posterior epispadias)

• Varied continence - depends on location

Treatment: surgical reconstruction

Question 127

Exstrophy of the Bladder

Definition, Pathophysiology, Clinical Manifestations, Treatment

Answer 127

Definition: rare, extensive congenital disorder where bladder herniates through the abdominal wall. Bone part of pelvis remains open, posterior portion of bladder mucosa is exposed through abdominal opening and is bright red

• Cloacal exstrophy: most severe and rare form of bladder exstrophy (intestine and spine involved)

Pathophysiology: caused by intrauterine failure of abdominal wall and mesoderm of anterior bladder to fuse. Rectus muscles below umbilicus are separated, pubic rami (bony projections) are not jointed. In girls, clitoris is divided into two parts with urethra in between

Clinical Manifestations:

• waddling gait (initially when they learn to work) but then corrected via compensation
• urine seeping onto abdominal wall from ureter causing constant urine smell and excoriation of surrounding skin
• Exposed bladder mucosa hyperemic and edematous, bleeds easily and painful

Treatment: surgery within the first year. Ideally bladder and pubic defect closed <72h birth

Question 128

Bladder Outlet Obstruction

Answer 128

Definition: obstruction at base of bladder/bladder neck/ Caused by:

• Urethral valve: thin tissue membrane that occludes urethral lumen and obstructs urinary outflor in males
• Urethral polyps: rare growths in children

Question 129

Ureteropelvic Junction (UPJ) Obstruction

Secondary UPJ Obstruction

Answer 129

UPJ Obstruction

Definition: blockage of the tapered point where renal pelvis transitions into ureter. Most common cause of hydronephrosis in neonates

Cause: mostly due to intrinsic malformation of smooth muscle or ureothelial development producing obstruction

Secondary UPJ Obstruction

• caused by kinking or secondary scarring from high-grade vesicoureteral reflux
• increased risk for those who have UPJ obstruction

Question 130

Ureterovesical junction obstruction

Answer 130

obstruction of the distal ureter causing dilation of the entire ureter, renal pelvis, and calyceal system

Question 131

Ureterocele

Answer 131

a cystic dilation of the intravesicle ureter; swelling at the bottom of the one of the ureters

Question 132

Define the following terms:

Renal aplasia

Hypoplastic Kidney

Renal dysplasia

Answer 132

Renal aplasia: kidney is absent, does not grow

Hypoplastic kidney: small kidney with decreased number of nephrons

Renal dysplasia: abnormal development of the kidney likely due to abnormal differentiation of renal tissues

Question 133

Polycystic Kidney Disease (PKD)

Definition, Pathophysiology, S/S

Answer 133

Definition: autosomal dominant disease OR autosomal recessive (depending on gene affected) where kidneys have multiple cysts interfering with renal function

Pathophysiology: Defects in the formation of epithelial cells and their cilia result in cyst formation in all parts of the nephron. Cysts in other organs, including the liver, pancreas, and ovaries, may occur.

S/S: HTN, aortic and intracranial aneurysms, and heart valve defects

Question 134

Renal Agenesis - Unilateral and Bilateral

Answer 134

Definition: absence of one or both kidneys. May be unilateral or bilateral, random occurrenc eor hereditary & can occur alone or with other disorders

Unilateral renal agenesis: usually L kidney absent, more often in males. Other kidney is normal so can be a normal healthy life. After several years, volume of good kidney may be 2x normal size to compensate. Risk of “hyperfiltration injury” due to decreased number of nephron, which may lead to proteinuria, HTN, CKD

Bilateral renal agenesis: rare, incompatible with extrauterine life. 75% are males. Oligohydramnios (low amniotic fluid) leads to inadequate fetal urine production which leads to underdeveloped lungs and Potter syndrome (wide-set eyes, parrot-beak nose, low set ears, receding chin). ~40% born stillborn. Usually no more than 24 hours after birth before death sets in because of pulmonary insufficiency.

Question 135

Glomerulonephritis

Answer 135

inflammation of the glomeruli characterized by hematuria, edema, and hypertension. The cause is unknown but is often immune mediated.

Question 136

Acute Poststreptococcal Glomerulonephritis (APGN)

Definition, Pathophysiology, Clinical Manifestations, Treatment

Answer 136

Definition: onst of the most common immune complex-mediated renal diseases in children, usually occurs after a throat/skin infection with strain group A β-hemolytic streptococci

Pathophysiology; Glomerulonephritis develops with the deposition of antigen-antibody complexes in the glomerulus. The antigen-antibody complex activates complement and the release of inflammatory mediators that damage endothelial and epithelial cells lying on the glomerular basement membrane. Damage to the glomerular basement membrane leads to hematuria and proteinuria.

Clinical Manifestation: Sx onset 1-2 weeks after URTI (more common during cold weather) and up to 6 weeks after skin infections

• child has hematuria, proteinuria, edema, renal insufficiency
• oliguria
• HTN due to increased vascular volume - if acute, may cause headache, vomiting, somnelence, other CNS effects
• dyspnea, tachypnea, enarlged tender liver

Treatment: disease usually runs its course in 1 month but may still have residual urine abnormalities up to 1 year later. Supportive treatment and symptom specific

Question 137

Immunoglobulin A (IgA) Nephropathy

Definition, Clinical Manifestations, Treatment

Answer 137

Definition: most common form of glomerulonephritis and occurs more often in males. Characterized by deposits of IgA and complement proteins in mesangium of glomerulus

• Henoch-Schönlein purpura nephritis: particular form of IgA nephropathy that involves systemic vasculitis

Clinical Manifestations: recurrent gross hematuria x RTI

• In Henoch-Schönlein purpura nephritis, palpable purpura, abdo pain, arhtralgia, hematuria, and/or proteinuria

Treatment: supportive with some recovering fully. 20% will require dialysis and transplantation

Question 138

Nephrotic Syndrome

Definition, Demographics, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment

Answer 138

Definition: term that describes a symptom complex characterized by proteinuria, hypoproteinemia, hyperlipidemia, and edema. Changes to glomerular wall permeability to protein.

• Primary (idiopathic) nephrotic syndrome
• Secondary nephrotic syndrome: resulting from systemic disease/other cause
• Congenital nephrotic syndrome (Finnish type) - caused by an autosomal recessive mutation of gene that encodes an Ih-like protein (nephrin) at podocyte slit membrane

Demographics: more common in children than in adults. Primary nephrotic syndrome - found mostly in preschool-age children (peak incidence 2-3 y.o., rare >8 y.o. Boys affected more.

Pathophysiology: most common causes in children are:

• Minimal change nephropathy (MCN)/lipoid nephrosis: fusion of glomerular podocyte foot processes due to an immune mechanism (however true etiology unknown). Leads to loss of -ve charge, increased permeability within the glomerular capillary wall leading to albuminuria. Leads to low plasma oncotic pressure so sodium retention occurs and edema. Hyperlipidemia as well which leads to fat in urine, reulting from increased hepatic lipid synthesis and decreased plasma lipid catabolism
• Focal segmental glomerulosclerosis (FSGS): segmental loss of glomerular capillaries with mesangial matrix proliferation and adesion of capillaries to Bowman capsule

Clinical Manifestations: insidious onset. Periorbital edema (first sign) that’s most noticeable in the morning and subsides during the day as fluid shifts to abdomen, genitalia, LE. Diminiahed, frothy, or foamy UO. If pronounced edema, then ascites, respiratory difficulty from pleural effusion, labial/scrotal swelling.

• Edema of instestinal mucosa: diarrhea, anorexia, poor absorption
• Malnutrition from malabsoprtion and protein loss: pallow, shiny skin with prominent veins
• Increased risk of infection
• Irritability, fatigue, lethargy common
• Finnish type: presents with heavy proteinuria, hypoproteinemia, edema in first 3 mos of life. Require albumin infusion and diuretics.

Diagnosis: findings of proteinuria, hyperlipidemia, and edema. Kidney biopsy.

Treatment:

• Glucocorticosteroids (prednisone)
• Low sodium well-balanced diet
• Good skin care
• Diuretics if edema becomes problematic
• Potentially immunosuppressants for those who have frequent relapses and resistant to steroid therapy

Question 139

Hemolytic Uremic Syndrome (HUS)

Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment

Answer 139

Definition: acute disorder characterized by hemolytic anemia, thrombocytopenia (low platelet levels), and acute renal failure. The most common cause of renal failure in chidlren. Most often occurs in infants and those <4 y.o.

Pathophysiology: associated with bacterial and viral agents and endotoxins (esp E. coli). Endothelial lining of glomerular arterioles become swollen and occluded with platelets and fibrin clots. Narrowed vessels damage passing RBCs which are then removed by the spleen causing acute hemolytic anemia. Fibrinolysis occurs on the precipitated fibrin causing fibrin split products to show up in serum and urine. Platelet thrombi develop within microcirculation (damaged vessels), and platelet removal produces thrombocytopenia. Occlusion leads to altered renal perfusion adn renal insufficiency/failure.

Clinical Manifestations:

• Prodromal GI illness - fever, vomiting, diarrhea and potentially URTI occur 1-2 weeks prior to HUS onset
• Symptom free for a couple days (1-5 days) then suddent onset of pallor, bruising or purpura, irritability, oliguria
• Others: slight fever, anorexia, vomiting, diarrhea (water and blood stained), abdo pain, mild jaundice, circulatory overload
• CNS involvement: seizures, lethargy
• Renal failsure apaprent within the first few days of onset. Causes metabolic acidosis, azotemia, hyperkalemia, and HTN

Diagnosis: past medical history, presenting symptoms, urine and blood analysis

Treatment: supportive management. Dialysis if renal failure occurs. Blood transfusions required for adequate Hb levels. If not responsive to tx, may need to remove spleen. 70% of children recover completely. May have long term consequences (renal - HTN, proteinuria, CKD, ESKD; non-renal - DM)

Question 140

Nephroblastoma (Wilms tumor)

Definition, Pathogenesis, Clinical Manifestations, Diagnosis, Treatment

Answer 140

Definition: rare embryonal kidney tumor arising from undifferentiated mesoderm. Most dx are <5 y.o. Represents 5% of childhood cancers. Peak incident 2-3 y.o. Possible increased risk with maternal preconception toxin exposure (eg. pesticides).

Pathogenesis: can be sporadic or inherited (autosomal dominant. 18% of those with nephroblastoma also have other congenital abnormalities:

• Aniridia - lack of an iris in the eye
• Hemihyperplasia - asymmetry of the body
• genitourinary malformations - horseshoe kidneys, hypospadias, ureteral duplication, polycystic kidneys

Children with both congenital anomalies and nephroblastoma are more likely to have the inherited bilateral form of the disease

Clinical Manifestations: asymptomatic abdominal mass before 5 y.o. (udsually discovered by child’s parent noting abdominal swelling). Child appears healthy and thriving. Other S/S: bague abdominal pain, hematuria, anemia, fever. HTN from excessive renin secretion by the tumor.

Diagnosis: Physical exam - firm, nontender, smooth tumor that is generally on one side of the abdomen. If palpable past the midline of abdomen, may be large or arising from a horseshoe/ectopic kidney. Surgical biopsy and imaging studies. Most common sites of metastasis are lymph nodes; less common - lungs, liver, brain, bone

Treatment: surgery, or chemo and then surgery. Radiation for those with higher stages of disease. Survival is good (80% +) but may have consequences down the road like CHF, renal failure, HTN

Question 141

UTIs - Children

Demographics, Types, Clinical Manifestations, Diagnosis, Treatment

Answer 141

Demographics: rare in newbornws. Increased risk in those with congenital renal abnormalities and noncircumcised males. Most common in 7-11 y.o. girls due to perineal bacteria (esp E. coli) ascending urehtra. Also increased risk if sexually active.

Types:

• Cystitis - bladder infection. Results in mucosal inflammation and congestion. Causes destrusor muscle hyperactivity and decrease in bladder capacity = urgency and frequency. May also cause distortion of ureterovesical (UV) junction which may cause urine reflux/up ureters leading to acute/chronic pyelonephritis
• Acute & Chronic pyelonephritis

Clinical Manifestations: Infants may be asymptomatic or develop fever, lethargy, abdominal pain, vomiting, diarrhea, asymptomatic jaundice. Children may have fever of unjnown origin, frequency, urgency, dysuria, incontinence in a previously dry child, flank or back pain, sometimes hematuria.

Diagnosis: urine culture

Treatment: Sx relief in 1-2 days with antibiotics, 2-4 days or longer course for UTIs

Question 142

Vesicoureteral Reflux (VUR) - Children

Definition, Demographics, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment

Answer 142

Defintion: retrograde flow of urine from bladder into the kidneys, ureters or both. Allows infected urine from bladder to reach the kidneys

Demographics: occurs more often in girls (10:1 ratio). Actual incident unknown due to VUR often going undiagnosed.

Pathophysiology: A congenital abnormality causes the submucosal tunnel and ureter to be shorter than normal which allows reflux from the rising pressure of the filling bladder. Urine sweeps up into the ureter and then flows back into the empty bladder. Reflux increases infection risk as it prevents complete emptying of the bladder and is giving it a reservoir for infection. Bladder filling can cause so much pressure that the urine gets pushed up into the renal pelvis and calyces, leading to pyelonephritis. Reflux may be bilateral or unilateral, graded as such:

• Grade I: reflux into a nondilated distal ureter
• Grade II: reflux into the upper collecting system without dilation
• Grade III: reflux into a dilated ureter or blunting of calyceal fornices
• Grade IV: reflux into a grossly dilated ureter and calyces
• Grade V: massive reflux with urethral dilation and tortuosity and effacement of the calyceal details

Clinical Manifestations: may be asymptomatic or have recurrent UTIs, unexplained fevers, poor grwoth and development, irritability and feeding problems. Family hx may reveal VUR or UTIs.

Diagnosis: Hx of recurrent UTIs and other symptoms & examine urine movement outflow (voiding cystourethrogram - VCUG)

Treatment: prevention and treating infection. May spontaneousl resolve in grades I-III in 50 to 80% of children <5 y.o. 20% in grades IV and V will resolves. Recurrent infection may require procedures to stop refluxing ureter.

Question 143

Urinary Incontinence - Children

Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment

Answer 143

Definition: aka enuresis. Involuntary passage of urine by a child who is beyond the age when voluntary bladder control shouldve been acquired (i.e. accomplished by most before 5 y.o.).

Pathophysiology: combination of factors

• Organic causes: UTIs, neurological disturbances, congenital defects of the meatus, urethra, bladder neck, & allergies
• Factors that increase normal UO: DM and DI, or those that impair concentrating ability like CRF or sickle cell disease
• Maturation delays
• Sleep patterns: altered sleep arousal or OSAS
• Psychosocial stress: like a new sibling
• Genetics
• Others: perinatal anoxia, CNS trauma, seizures, ADHD, developmental delay, imperforate anus, bladder trauma or surgery, obesity, and occult spinal dysraphism
• Constipation frequently present in children with urinary incontinence

Diagnosis: thorough history, voiding diary, physical exam, urinalysis. Potential urodynamic flow studies and imaging.

Treatment: Education for family and child depend on underlying cause.

• For datyime incotinence: behavioural therapy (timed voiding), fluid management, treatment of constipation, UTIs, other conditions if present, meds
• Enuresis: enuresis alarms or other meds

Question 144

Types of Urinary Incontinence

Answer 144

1) Daytime incontinence: wetness occuring during the day

2) Enuresis: nighttime wetting

3) Primary incontinence: child has never been continent

4) Secondary incontinence: child has been continent for at least 6 mos before wetting recurs