Renal Disorders

Question 1

Major Functions of Kidney

Answer 1

-Excretion of Metabolic Wastes >Nitrogenous wastes —>Urea, ammonium, uric acid, and creatinine -Maintain Water-Salt Balance >Kidneys maintain appropriate water-salt balance >Regulating blood pressure —>Renin/angiotensin/aldosterone -Maintain Acid-Base Balance >Kidneys monitor and help control blood pH by excreting hydrogen ions and producing/reabsorbing HCO3- -Secretion of Hormones —>Erythropoietin —>Activation of vitamin D

Question 2

Evaluation of Renal Function -

Answer 2

-Urinalysis: Color/ clarity, pH, specific gravity, urine protein, blood, urine microscopy (RBC, WBC’s, bacteria, urinary casts) -Glomerular Filtration Rate: Creatine clearance, 24 hr urine protein, 24 hour urine protein, 24 hour urine volume -Blood tests: blood urea nitrogen (BUN), and serum creatinine

Question 3

Two congenital Kidney Disease

Answer 3

-Renal -Polycystic kidney disease

Question 4

Renal Agenesis

Answer 4

-A failure of the kidneys to develop -Can occur randomly or be hereditary -Males are affected more than females -Often associated with other abnormalities —>(skeletal, cardiac, GI, respiratory, CNS)

Question 5

Renal Agenesis Incidences

Answer 5

-Unilateral (only have one kidney) —>Incidence is about 1 in 1000 live births —>Functional kidney undergoes compensatory hypertrophy -Bilateral (Potter syndrome) —>Incidence is about 1 to 4 in 10k live births —>Infants rarely live a few hours

Question 6

Polycystic Kidney Disease

Answer 6

• Group of inherited renal disorders characterized by fluid filled sacs or segments in the tubular structures of the kidney
• Two versions

>Autosomal Dominant (ADPKD)

>Autosomal Recessive (ARPKD)

Question 7

ADPKD vs ARPKD

Answer 7

Question 8

ADPKD Incidence

Answer 8

• 1 in 400 to 1000 live births
• Two topes that produce nearly identical renal and extra-renal disease
• Type 1 (85% of cases) caused by PKD1 gene (polycystin-1)
• Type 2 (15% of cases) caused by PKD2 gene (polycystin-2)
• Renal function is normally retained until the fourth or fifth decade of life
• Kidney cysts will enlarge to such a degree that the kidney interstitium is compromised, leading to kidney failure
• Renal failure

–>Type 1: 35% by 50 and 90% by 70

–>Type 2: 5% by 50 and 45% by 70

Question 9

ADPKD-Proposed Mechanism

Answer 9

1-Polycystin-1 and 2 are located within primary cilium found in the kidney tubules

—>Defects may disrupt intracellular Ca2+ levels

2-Abnormal basement membrane structure and function

3-Increased production of fluid by cells forming the cyst

Question 10

Other effects of ADPKD

Answer 10

• ADPKD patients may also form cysts in the liver, pancreas, ovaries, spleen, and large bowel
• Aneurysms can develop in the brain
• Heart valves can become floppy and lead to murmurs

Question 11

Autosomal Recessive-PKD

Answer 11

• Defect in the PKHD1 gene (fibrocystin)
• Much faster progression and is diagnosis prenatally or in infacy
• About 25% die within the first few months of live: Due to severe renal failure, pulmonary hypoplasia, severe liver fibrosis

Question 12

Renal/Urinary Trac Infectious Disorders

Answer 12

• Bladder infections (cystitis)
• Acute pyelonephritis
• Chronic pyelonephritis

Question 13

Unrinary Tract Infection (UTI)

Answer 13

• Infection of the urinary epithelium
• Can occur any where along the urinary tract

—>Cystitis (bladder)

—>Pyelonephritis (upper urinary tract)

—>Lower UTI: Urine is cloudy, foul smelling & high in nitrites and leukocytes

-Risks: female, obstruction, urine stasis, high pH

Question 14

Causes of Urinary Tract Infections

Answer 14

• Bacteria: E.coli (80%), Staph, Enterobacter, Klebsiella, Proteus
• Fungal: Candida
• Parasitic: Schistosomiasis (infects 200 million people worldwide, rare in the US)

Question 15

Sources of Urinary Tract Infections

Answer 15

• Ascending infection:
  1) Colonization of the distal urethra by coliform bacteria
  2) migration from urethra to the bladder
  3) Multiplication in the bladder
  4) Vesicoureteral reflux
  5) Intrarenal reflux

Question 16

Cystitis

Answer 16

• An inflammation of the bladder
• Manifestations: Frequency, dysuria, uregency, and lower abdominal and/or suprapubic pain
• Treatment: Antimicrobial therapy, increased fluid intake, avoidance of bladder irritants, urinary analgesics

Question 17

Acute Pyelonephritis

Answer 17

• Bacterial infection of the renal parenchyma, pelvis and ureters
• The inflammatory resposne results in arterial constriction and edema in the affected areas
• Renal scarring and subsequent chronic disease may be prevented by rapid treatment to limit the infection

-Risk Factors

1) Any Urinary tract obstruction
2) Pregancy
3) Cathererization
4) Kidney Transplant-Polyoma virus
5) Diabetes mellitus

Question 18

Symptoms of Urinary Tract Infection (UTI): Compare and contrast Pyelonephritis & Cystitis

Answer 18

Question 19

Chronic Pyelonephritis

Answer 19

• Pathological changes in the kidney as a result of result of recurring or presistent infection
• Chronic interstitial inflammation develops with lymphocytic and plasma cell infiltration of the kidney tissue
• Fibrosis of the interstitium (including tubules) results in decreased function of the nephron

Question 20

Glomerulonephritis

Answer 20

• Inflammation of the glomeruli
• Most common cause of chronic renal disease and renal failure
• May be either acute or chronic in nature
• Can be a primary or secondary condition: (SLE, diabetes mellitus)

Question 21

Etiology and Pathogenesis of Glomerular Injury

Answer 21

• Three Major triggering events
  1) Immunologic-Most common
  2) Non-Immunologic: Diabetes, hypertension, toxins, drugs
  3) Hereditary: Alport Syndrome

Question 22

Glomerular Inury

Answer 22

• Capillaries of the glomeruli are arranged in lobules and are supported by a stalk consisting of mesangial cells
• Structural changes of the glomerular capillary membrane due to injury

–> Endothelial cells

–>Basement membrane

–> Epithelial podocytes

1) Hpercellularity
2) Basement membrane thickening
3) Sclerosis & Fibrosis

—>Decrease in Glomerular blood flow and GFR; Increase in vascular permeability

Question 23

Nephritic Syndrome

Answer 23

• Hematuria
• Proteinuria
• Systemic Edema: Hypertension–> Water and Salt retention
• Oliguria

—>Oliguria: urine output <30ml/hour or x<400 ml/ day

-Azotemia

Question 24

Acute Nephritic Syndrome

Answer 24

• Typically due to Deposition of immune complexes
• Acute Post Infectious Glomerulonephritis

–>Group A B-hemolytic streptocci of the pharynx

-May also be associated with SLE

Question 25

Immunoglobulin A Nephropathy (Berger Disease)

Answer 25

- Characterized by deposition of IgA containing immune complexes to glomerular mesangial cells - Cause is unknown - Usually presents with hematuria 2 to 4 days following respiratory or GI infection - Very slow progression with about 50% of individuals only having a single episode

Question 26

Rapidly Progressive Glomerulonephritis

Answer 26

- Severe glomerular injury that typically does not have a specific cause - Rapidly progresses often within a matter of days to weeks - Classic example is Goodpasture Syndrome

Question 27

Goodpasture Syndrome

Answer 27

-IgG autoantibodies destroy the GBM and also the pulmonary alveolar membrane --\>Non-collagenous domain of the alpha-3 chain of the collagen type IV -Cause is unknown: Viral, hydrocarbon exposure, genetics (HLA-DRB1)

Question 28

Hereditary Nephritis Alport Syndrome

Answer 28

- Genetic disorder resulting in the production of abnormal collagen type IV in the GBM - Leads to defective filtration of the GBM - 80% of cases are X-linked dominant trait - Characterized by heavy hematuria - Also associated with deafness and various eye disorders

Question 29

Glomerular Lesions Associated With Systemic Disease

Answer 29

- Systemic Lupus Erythematous: Glomerulonephritis--\>Associated with immune complex deposition - Hypertensive Glomerular Disease: Chronic hypertension can cause sclerotic changes to the renal arterioles (benign arterial hypertension) - Diabetic Glomerulosclerosis

Question 30

Diabetic Glomerulosclerosis

Answer 30

- Pathogenesis: 1) Metabolic defect 2) Nonenzymatic glycosylation of ECMs 3) Hemodynamic changes - Eventually leads to thickening/scarring of the GBM and the mesangial maxtrix leading to a decrease in GFR

Question 31

Nephrotic Syndrome

Answer 31

- Nephrotic syndrome can be caused by a variety of glomerular disorders - Increased glomerular capillary permeability results in massive proteinuria (\>3.5 gm/day) - Common manifestations: hypoalbuminemia, edema, hyperlipidemia and altered immune function.

Question 32

Chronic Glomerulonephritis

Answer 32

- A continuous hematuria and proteinuria leading to a slow degeneration in glomerular and renal functino - Chronic GN progresses to hypertension, kidney atrophy and scarring and eventual renal failure

Question 33

Pyelo- vs Glomerulonephritis

Answer 33

pyelonephritis glomerulonephritis ## Footnote Cause: infection inflammation S/S CVA, fever decreased GFR Prognosis good not as good Treatment antibiotics anti-inflammatory

Question 34

Renal Failure

Answer 34

2 types -_Acute Renal failure:_ \>Pre-renal (decreased perfusion) \>Intra-renal (tubular necrosis) \>Post-renal (obstruction of urine flow) -_Chronic renal failure_

Question 35

Acute Renal Failure

Answer 35

_-Acute renal failure:_ an abrupt decline in renal function (x\<400mL/day, oliguria). Elevated BUN and plasma creatinine levels. -May be reversible if detected and treated early

Question 36

Management of ARF

Answer 36

-Prevention: \>Assess for adequate renal perfusion \>Avoid nephrotoxins (heavy metals) \>Early treatment of obstruction -Treatment: \>Acute dialysis \>Fluid management

Question 37

Chronic Renal Failure

Answer 37

- The irreversible loss of renal function over time which leads to eventual end-stage renal failure (x\<10% renal function). - Common causes: diabetes, hypertension - Increase in BUN and creatinine as a renal function (GFR) declines below 50%

Question 38

Stages of CRF

Answer 38

1-Diminished Renal Reserve \>GFR is about 50% of normal \>Serum BUN & creatine are normal \>Patients are asymptomatic 2-Renal Insufficiently \>GFP is 20%-50% of normal \>Azomtemia appears \>Anemia & hypertension 3-Chronic Renal Failure \>GFR is less than 20% of normal \>Edema, hyperkalemia & metabolic acidosis \>Uremic syndrom may occur 4-End stage renal Disease \>GFR is less than 10% of normal \>Uremic Syndrome \>Mulitple organ failure

Question 39

Osteodystrophy

Answer 39

Decrease in active Vitamin D --\> Decrease serum calcium --\> Increase parathyroid hormone ---\> Bone resorption --\> Increase serum calcium Scarificing Bones for calcium Another Trigger- Decrease in GFR --\>Increases Serum PO4 --\> Increases parathyroid hormone Metabolic acidosis= bone resorption

Question 40

Explain Uremic Syndrome

Question 41

Management of CRF

Answer 41

- Restrict fluids, Na+, K+, PO4 - Low protein diet - Phosphate binding antacids - Vitamin D supplementation - Dialysis - Renal Transplant

Question 42

Severity of obsturction depends on

Answer 42

- location of obstructive lesion - Whether one or both urinary tracts are involved - severity (completeness) of the blockage - Duration - Nature of obstruction

Question 43

What are the Nephrolithiasis Risk factors?

Answer 43

- Male - Between ages 20-40 - Inadequate fluid intake (biggest contributor): Concentration of solute in urine - Living in desert or tropical region: Temperature, humidity, fluid, and dietary patterns - Lack of exercise - pH of urine

Question 44

Nephrolithiasis: Pathophysiology

Answer 44

- Supersaturation of one or more salts in the urine - Precipitation of the salt - Crystallization - Absence of stone inhibitors ---\>Tamm-Horsfall protein ---\>Potassium Citrate -Treatment

Question 45

Types of Stones

Answer 45

-Calcium stones (-75% of all urinary stones) ---\>comprised of Ca2+ oxalate, and or Ca2+ phosphate -Magnesium (20%) ---\>Magnesium ammonium phosphate (Struvite) - Uric Acid Stones (5%) - Cystine (1%)

Question 46

Neurogenic bladder

Answer 46

- Lower Urinary Tract Obstruction - General term for bladder dysfunction caused by neurological disorders - Lesion associated with upper motor neurons result in dysynergia - Lesions associated with lower motor neurons results in underactive atonic (flaccid) bladder function with a loss of sensation

Question 47

Bladder Tumors

Answer 47

- Bladder tumors comprise 3% of all maligant tumors - The risk for bladder cancer is hiher for men greater than 60 years old and who smoke and or have been exposed to aniline dyes - Bladder cancer is highly associated with mutations in the p53 tumor suppressor gene

Question 48

Renal Cell Carcinoma

Answer 48

- Makes up about 2% of all maligancies and 85% of all renal neoplasms - Adenocarinoma - Tumors tend to originate in the epithelium of the PCT - Risk Factors: ---\>Exposure to petroleum products ---\>Asbestos ---\>Cigarette smoke ---\>Obesity ---\>Long term analgesic use ---\>Hypertension ---\>High protein diet ---\>AD-PKD ---\>Family history

Question 49

Wilm's Tumor (nephroblastoma)

Answer 49

-Caused by a mutation of the Wilm's tumor suppressor gene ---\>WT1 gene, chromosome 11 ---\>WTX gene, X chromosome -This defect results in abnormal growth of kidney tissue resulting in abdominal mass ---\>Composoed of blastemic, stromal and epithelial cells.