Introduction to Clinical Medicine

Reproductive-Renal systems

Student Case Studies

Prepared by:
Robert W. Wilhoite M.D.
Edited by Patrice Thibodeau, M.D.
 Case # 1
• This 28 year old married woman
complains of severe dysmenorrhea,
dyspareunia and midline lower
abdominal pain x 2 years.
• Her menstrual cycle is irregular
• She has been unable to become pregnant
during her five years of marriage.
 Problem List
•Dysmenorrhea
•Dyspareunia
•Infertility
•Midline lower abdominal pain
•Irregular periods
What other Hx else do you want to know?
What PE do you want to do?
DDx?
 Differential Dx for
Dysmenorrhea Infertility
• Primary Dysmenorrhea • Is papa the problem?
• Secondary Dysmenorrhea • Anatomic causes
– Endometriosis – Cervical stenosis, prior surgical
– Chronic PID treatment, poor cervical mucus
– Adenomyosis – Uterine adhesions, fibroids, polyps,
– Ectopic pregnancy endometritis
– – Hx of PID, endometriosis pelvic
Fibroids
adhesions
– Ovarian cysts
– Intrauterine or pelvic
• Ovulatory factors
adhesions – Pituitary or hypothalamic insuff
– Cervical stenosis – PCOS
– Use of IUD – Hyperprolactinemia
– Premature ovarian failure, Turner’s
– Thyroid disease
 Diagnosis and Treatment
of Primary Dysmenorrhea
• More likely 1° dysmenorrhea if
– began younger then 25 yo,
– not associated with abn uterine bleeding
– absence of dyspareunia
– no progression of severity
– Nml Pelvic exam
• 1° Dysmenorrhea treated with NSAIDS and OCP’s
• Our patient’s problems started at age 26 and is associate
with abn menses and dyspareunia. Thus likely 2° cause.
What is your primary dx?
PID as cause of 2° dysmenorrhea
• Most common in 15-25 yo
• Pain shortly after menses, worsens during
coitus, 1/3 have abn uterine bleeding
• If suspect then work up do pelvic and sample
collection
– PE  purulent discharge, +CMT and adnexal
tenderness
– Treat PID as previously reviewed
Endometriosis • Common

Hx/PE •
•
Menses-related pelvic pain and at other times too
Dyspareunia, Infertility
• Pain may not be relieved with NSAIDS,
progressive worsening of sxs
• PE
– Tenderness on vaginal exam
– Nodules in posterior fornix
– Uterosacral ligament abn (nodularity, thickening,
tenderness on rectovaginal exam)
– Lateral displacement of cervix*
– Cervical stenosis
– Adnexal enlargement from an endometrioma
Endometriosis
Diagnosis
• Imaging
– Transvaginal US to
locate ovarian cysts
(enodmetriomas), nodules Endometrioma of the right ovary
on rectovaginal septum
– Abd US can show abd
wall endometriosis
• Laparoscopy and biopsy
– See studding with
implants

Lapraroscopy
Endometriosis – Fallopian Tube
 Endometriosis
Treatment
• Mild to moderate pain and no US evidence of
endometrioma  try NSAIDs and OCPs
• Severe symptoms  GnRH agonist (ie
leuprolide) + “add-back” estrogen to minimize
the hypoestrogenic effects of GnRH agonist.
• Sxs unresponsive to medical therapy 
Surgical treatment (laparoscopy) to destroy
implants and remove endometriomas
 Adenomyosis
• Usually >35 yo
• Pain is often limited to
menses
• +Dyspareunia
• Endometrial glands and
stroma are present within the
uterine musculature not just
endometrium where they
belong!
• Causes enlarged uterus and
irregular bleeding
 Case 1

Final diagnosis

Endometriosis
 Case # 2
• This 26 year old Olympian shotput thrower has had
normal menstrual periods since her menarche at
age 12.
• However, for the last six months she has
experienced progressive oligomenorrhea, weight
gain, facial hair growth and increased acne.

• What else do you want to know?

• What are you looking for on PE?
 Case # 2
• Physical exam revealed
upper back and facial
hirsutism
• Nml visual fields
• Pelvic exam reveals:
bilateral ovarian
enlargement and a
normal size uterus.

• Problem list?
 Problem List
• Oligomenorrhea
• Weight gain
• Hirsutism
• Acne
• Bilateral ovarian enlargement

• Your thoughts?
• DDx for hirsutism, oligomenorrhea?
What conditions may be associated
with oligomenorrhea
– Premature menopause (high FSH and LH
levels)
– Rapid weight loss or obesity
– Discontinuation of contraceptives
– Pituitary adenoma (elevated prolactin)
– Hypo or hyperthyroidism
– Infrequent ovulation as seen in PCOS
 What is your work up for pt?
• Check total
testosterone (should be
elevated)
• Check 17-
hydroxyprogesterone
(to rule out nonclassic
CAH)
• Order transvaginal
ultrasound (TVUS)
What is your interpretation of the biopsy of ovary??
Polycystic ovary syndrome
Classic findings PCOS/PCOD (in a Stein-
Leventhal syndrome )
– Hyperandrogenism
• Hirsutism, acne, male-pattern hair loss
• Virilization (deepening of the voice, clitoromegaly)*
– Irregular menses ie Oligomenorrhea
– Infertility
– Metabolic issues
 Metabolic issues in PCOS

• Obesity and insulin resistance

– Hyperinsulinemia contributes to hyperadrogenism*
– Weight loss and reducing insulin resistance with metformin
helps decrease androgen levels.
• Metabolic syndrome and Dyslipidemia
• Nonalcoholic fatty liver disease
• Increased risk for Type 2 DM
• Sleep apnea
• Increase risk for coronary heart disease
 Etiology

– PCOS is a complex genetic trait whose

development is likely influenced to some
degree by environmental factors (eg, diet and
the development of obesity) and more
significantly by a number of different genetic
variants.
 Treatment?
• Encourage weight loss!
• OCP to manage hyperandrogenism and abn
menses
– Use OCP that has progestin with low androgen
activity
• Spironolactone (an antiandrogen) can help
with the hirsutism if OCP not enough
 Case 2

Final diagnosis

Stein-Leventhal syndrome
Polycystic Ovarian Syndrome
 Case # 3
• A 26 year old woman has noticed some
intermittent vaginal spotting for the past three
weeks. She is single, has had two different sexual
partners over the past 3 months.
• There is a past history of gonorrhea which
apparently responded to appropriate therapy.
More recently she has developed back pain and
right lower abdominal pain.

• What do you want to do for an exam?

 Case # 3
• Palpation of her abdomen revealed some mid-
line tenderness and rebound tenderness in the
RLQ. Bowel sounds are absent.
• A pelvic exam revealed a small quantity of
blood oozing from the cervix.

What labs would you order?

 Laboratory findings
– Hgb 8.6 (L)
– WBC 21,000
– Differential smear = shift to the left

Interpretation?
What is your problem list?
 Problem List
– Vaginal spotting by history
– History of gonorrhea
– Back and RLQ pain
– Absent bowel sounds and rebound tenderness
– Cervical spotting on exam
– Leukocytosis and anemia

What is your differential diagnosis?

 Differential Diagnosis?
– Acute appendicitis
– Acute PID
– Rupture of corpus luteum ovarian follicle
– Ruptured ectopic pregnancy
– Cystitis
– Renal calculus

– How to you proceed with your evaluations?

 How would you proceed in your
evaluation of this patient?
– Obtain past menstrual history
– Beta HCG level
– Cervical cultures
– Abdominal ultrasound
– Vaginal ultrasound
– Culdocentesis
 Case 3

Final Diagnosis

Ectopic tubal pregnancy

 Case # 4
• This 23 year old woman consulted her GYN physician for post-
coital bleeding.
• Gyne history: she is sexually active, uses a condom most of the
time and admits to intercourse with several different partners.
Menses began at age 14, regular up until 3 months ago.
• A pelvic exam revealed no abn vaginal discharge, adnexal
masses or tenderness, and no cervical motion tenderness.
There is a small hyperemic area at the squamocolumnar
junction; recto-vaginal exam was negative.
• A thin pap smear of the cervix was reported as ASCUS.
What is a thin prep pap smear?
Thin Prep – Liquid based cytology
 Thin Prep – Liquid based
cytology
• Liquid-based cytology systems allow testing for cytology,
HPV, gonorrhea, chlamydia, and trichomonas from a
single specimen.
 What are the most up to date cervical cancer
screening guidelines?

• Begin cervical cancer screening at age 21.

• Screening for ages 21-29 : cytology alone q 3 years
– Do not perform HPV testing in women less than 30 yo.*
• Screening for ages 30-64: Co-testing with cytology
and HPV testing every 5 years is preferred.
Cytology alone every three years is acceptable.
• Screen more frequently in pts with positive Pap or
high-risk HPV testing; HIV infection;
immunosuppression; DES exposure in utero; prior
hx of cervical cancer.
 When to stop testing for cervical cancer?

• Stop testing at age 65 for women with adequate** negative prior

screening, no CIN II or III in last 20 years.
• Pap smears not recommended for women with hysterectomy and
removal of cervix without precancerous lesions
 Back to the case…
Problem List
• Post-coital bleeding
• Hyperemic area at squamocolumnar
junction
• Sexual promiscuity
• Abn Pap smear - ASCUS
 Thought questions
• What is the meaning of the pap smear
reported as ASCUS?
– Atypical squamous cells of undetermined
significance.
• What is the present system for evaluating
cervical cytology?
 The Bethesda System
• A cytological classification method to evaluate epithelial
cell abnormalities of the cervix. (squamous cell and
glandular cells)
• Squamous Cells atypia
– ASCUS – atypical cells of undetermined significance
– LGSIL – low grade squamous intraepithelial lesion
• CIN grade I (histological classification)
– HGSIL – high grade squamous intraepithelial lesion
• CIN grade II and III (histological classification)
– Squamous cell carcinoma
Bethesda
Classification
of cervical
cytology
(Squamous and
Glandular)
• How would you proceed in your evaluation
of the 23 yo patient with AS-CUS on pap
smear?
 ASCCP Guidelines
Abnormality Age ≥ 25 Years Age 21-24 Years*

ASC-US •Reflex HPV testing •Repeat cytology at 12-month

•Repeat co-testing** at 3 years if HPV-negative intervals
•Colposcopy if HPV-positive •Colposcopy if ASC-H or HSIL at 12
months, or ASC-US or worse at 24
months
•Resume routine screening if 2
consecutive negative results

American Society for Colposcopy and Cervical Pathology (ASCCP)

 Colposcopy
• A magnifying instrument
designed to facilitate the
inspection of the vagina and
cervix (10-20 x mag)
• The cervix and vagina are
swabbed with acetic acid
(vinegar), which will turn
abn areas white. These areas
are biopsied.
 HPV infections
• Associated with high percentage of all cervical
dysplasia and cancers.
• There are 70 subtypes of HPV
• Types 6 and 11 cause genital warts and mild
dysplasia
• Types 16 and 18 cause high grade lesions
• Vaccines available to prevent cervical cancer and
vaginal and vulvar precancerous lesions caused by
types 6, 11, 16, 18,31,33, 45, 52, 58
Normal cervix
GROSS PATHOLOGY OF THE
CERVIC
Obtain pap smear from
endocervical junction
Extensive cervical erosion
Squamous cell carcinoma
Cervical squamous cell cancer
What is outlined in blue?
HISTOLOGY OF THE CERVIX
Histopathology of CIN
Cervical Biopsies
ASCUS
Koilocytes – HPV infection
Low grade squamous intraepithelial lesion LGSIL
HGSIL
HGSIL
Pap Smears
Pap smear HGSIL
What are the risk factors associated with
cervical carcinoma?
– HPV infection – high risk types 16 & 18
– Cigarette smoking
– Early onset of sexual activity
– Multiple sexual partners
– History of sexually transmitted diseases
– Early age of pregnancy
Methods to prevent cervical
cancer
– Regular cytologic screening
– Limiting the number of sexual partners
– Use condom
– Stop smoking or exposure to second hand
smoke
– HPV vaccine which includes vaccine for 6, 11,
16, 18 subtypes and others in the HPV 9 valent
vaccine
 Case 4

Final diagnosis

ASCUS causing postcoital

bleeding
 Case # 5
• This 32 year old sexually active woman presents
with progressive lower abdominal pain for 3
months, fever and chills. More recently she
noticed RUQ pain and pleurisy. She also
complains of vaginal discharge and dyspareunia.
Denies cough or hemoptysis.
• Temp 38.5 Celsius. Lung exam is clear. Pelvic
exam shows some adnexal tenderness and a
purulent cervical discharge.
 Problem List
• Lower abdominal pain
• RUQ pain
• Fever and chills
• Dyspareunia
• Pleurisy
• Adnexal tenderness
• Cervical discharge
 What are your thoughts?
• Pelvic inflammatory disease (PID)
• Appendicitis
• Ectopic pregnancy
• Septic abortion
• Twisted or ruptured ovarian cyst
• Acute enteritis
• Acute endometritis
• Endometriosis
DDx for the RUQ pain (and pleurisy)?

• Cholecystitis
• Cholelithiasis
• Hepatitis
• Perihepatitis
• Perihepatic abscess
• Pulmonary Embolism
• RLL Pneumonia
 How would you proceed in your
evaluation of this case?
• CBC - ? Anemia, infection
• Sed. rate / CRP ? Infection
• NAAT of cervical discharge
• Pregnancy test - ? Pregnancy
• US or CT scan to evaluate the RUQ pain
depending on ddx
• Consider laproscopy (see next slide)
• (Consider D Dimer to r/o PE if intermediate
risk/CXR if suspect PNA)
Laparoscopy finding
Normal UTO
 What is your principal
diagnosis?

Pelvic Inflammatory disease

With perihepatitis (Fitz-Hugh-Curtis
syndrome)
 What are the potential
complications of PID?
• Infertility
• Tuboovarian abscess
• Ectopic pregnancy
• Chronic pelvic pain
• Peri-hepatitis (FHC syndrome)
 Case 5

Final diagnosis

Pelvic inflammatory disease and

Fitz Hugh Curtis Syndrome
Renal Cases
Quick Review
 What tests would you order in the
laboratory investigation of
• Blood Renal Disease
– BUN - Urine Analysis
– Creatinine Dip stickSG, pH, Blood, Protein, Glu,
– Creatinine clearance – GFR Ketones, Nitrites, Leukocyte esterase
evaluation (now part of the
BMP)
– Sodium/potassium/calcium
– Serum osmolality
• FENa
• Urine
– Urine osmolality - Microscopy
– Urine culture RBC’s, WBC’s, Casts, Crystals, oval bodies
 Histopathologic Evaluation of
Renal Disease….
• 1. Routine light microscopy including polarized
lighting

• 2. Immunofluorescence stains

• 3. Electron microscopy

Will see some of these in the cases

 Case # 6
• This 53 year old man has a long standing history of
hypertension. More recently he has experienced
an acute elevation of his blood pressure to 250/150.
He also complains of visual changes.
• Patient lost his job and health insurance 9 months
ago.

• What other questions do you have for the patient?

 Case # 6
• Patient lost his job and health insurance 9 months
ago and stopped taking his BP meds.
• He now manifests severe oliguria with a 24 hour
urinary output of 400 ml.

What PE would you do?

 Case # 6
• Physical exam reveals papilledema.
• No peripheral or periorbital edema
• No renal bruits

Labs?

• BUN of 92 (nml 8-20)

• Cr of 9 (nml 0.7-1.3)
• Bun/Cr about 10:1
• Urine microscopy pending
 Problem List
• Past history of hypertension
• Acute elevation of BP due to discontinuation of
meds
• Papilledema
• Oliguria
• Azotemia (Elevated BUN)
• Elevated Creatinine
 Thought questions
What is your initial impression of the
patient’s clinical course?
– Hypertensive emergency with onset of AKI

How would you initially treat this patient?

– Lower his blood pressure!
 Thought questions
• How are the causes of AKI (acute kidney
injury) categorized?
 Classification of AKI
• Pre-renal
• Intrinsic
• Post-renal
 Prerenal
• Decrease in normal renal perfusion
– Hypovolemia
– Decreased cardiac output
– Reno-vascular disease ( e.g. renal artery
thrombosis or RAS)
– Systemic vasodilatation
– Renal vasoconstriction ( e.g. vasopressor drugs)
 Intrinsic
• Acute glomerulonephritis (AGN)
• Acute tubular necrosis (ATN)
• Acute interstitial nephritis (AIN)
• Tubular obstruction
 Post-renal
• Bilateral Ureteral obstruction
– Stone or tumor
• Bladder neck obstruction
– tumor
• Urethral obstruction
– Prostatic hypertrophy
– Bladder thrombus
– Renal calculus
 Thought questions
• What is the DDx for the AKI in this patient?
• Would you like to ask any other questions?
What tests would you order in attempting
to make a diagnosis in this man?

– Recheck BUN/Creatinine  confirmed azotemia

– eGFR  low
– Urine electrolytes
• In pre-renal failure urine Na and FENa is low (<10mg/dl) and
< 1% respectively; kidneys retain plasma sodium and water.
• With ATN- Una is > 40, FENa is >2%
• FENa (Fractional excretion of sodium)
– (Una x Pcr/Ucr x Pna) x 100
• FENa as 4%
– Urinary sediment analysis (microscopy)
• No RBC’s or WBC’s; + muddy brown casts; no crystals
– Renal biopsy (see next slide)
Two renal biopsies were performed.
What is your interpretation?
Slide # 1
Acute tubular necrosis

Slide # 2
 Thought question
• How do you explain the evolution of his acute
renal failure?
– Initially this patient had essential hypertension which
evolved into malignant hypertension after he
discontinued his BP medications
– He subsequently developed acute renal failure as a
result of acute tubular necrosis from poor renal
perfusion due to the malignant HTN.
 Case # 6

Final diagnosis
Malignant Hypertension
with
Acute Tubular Necrosis
BREAK!!
 Case # 7
• This 46 year old woman has a long standing
history of osteoarthritis for which she is taking
heavy doses of the NSAID diclofenac
• On PE, she was found to have a mild elevation
of her blood pressure to 146/90 and peripheral
and periorbital edema.
• Labs follow
 Laboratory results
•Serum protein = 4.6 (nml 6.0-
7.8)
•Albumin = 1.9 (nml 3.5-5.5)
•Urinalysis = 4 + protein
•24 hours protein excretion
= 3.8 gms (high)
•Total Cholesterol 290 (high)
Urine microscopy

How would you

summarize these
findings?
 Problem List
• History of osteoarthritis
• Heavy NSAID use
• Mild hypertension
• Generalized edema
• Urinalysis:
– Nephrotic range proteinuria (>3.5/24 hours)
– Hypoalbuminemia
– Lipiduria
 Thought questions
How do you explain the clinical findings?

Consistent with nephrotic syndrome

 What are the classic findings of
nephrotic syndrome? Pathophysiology?
• Heavy proteinuria
– Urine protein excretion of > 3.500 mg/24 hr =
nephrotic range
• Hypoalbuminemia
– Serum albumin < 3g/dL
– Due to urinary loss of albumin
• Peripheral/Periorbital Edema
– From increased Na absorption by the distal
nephron in response to low oncotic pressure
 What are other findings of
nephrotic syndrome? Pathophysiology?
• Hyperlipidemia*
– Due to combination of increased hepatic lipoprotein
synthesis in response to low plasma oncotic pressure,
diminished clearance, and decreased catabolism of
lipids (due to decreased activity of key enzymes such
as lipoprotein lipase and lecithin-cholesterol
acyltransferase)
• Lipiduria**
– Oval fat bodies or fatty casts seen on urine microscopy
– Represent lipoproteins reabsorbed by tubular epithelial
cells from the vascular supply with subsequent
shedding into the urine
 What are complications
nephrotic syndrome?
• Hypercoagulability – due to loss of natural
anticoagulants Pro C and ATIII and
upregulation of coagulation factors by the liver
in response to low oncotic pressure
• Infection – due to urinary loss of
immunoglobulin
• Vit D def, iron def, thyroid disorders due to
loss of binding proteins
 DDx for nephrotic syndrome
• Idiopathic/Primary causes
– Membranous glomerulopathy (MG) – most common in whites
– Focal segmental glomerulosclerosis (FSGS) – most common in blacks
– Minimal change glomerulopathy (MCG) – most common in kids
– Membranoproliferative glomerulonephritis (MPGN)
• Secondary
– Diabetes Mellitus (FSGS)
– Infection – HIV, parvovirus (FSGS); Hep B and C, malaria syphilis
(MG); mono (MCG)
– Autoimmune disease –SLE (MG, MGPN)
– Malignancies-bladder, breast, colon, lung, pancreas, prostate, stomach,
lymphomas, leukemia (MG); Hodgkin’s, thymoma’s (MCG)
– Drugs- NSAIDs (MG and MCG), gold salts TNF a-inhibitors (MG);
heroin use (FSGS)
– Thyroid disease (MG)
Primary Causes of Nephrotic Syndrome
Secondary Nephrotic Syndrome
Secondary Nephrotic Syndrome
Review of the idiopathic
(primary) causes of
Nephrotic Syndrome
Membranous Glomerulopathy
• Most common cause of idiopathic nephrotic syndrome
in adult white population
• Pathogenesis of idiopathic MG: Circulating
autoantibodies directed to podocyte surface antigens
activate complement and damage the glomerular
basement membrane; in situ formation of immune
complexes; BM thickening with little to no cell
proliferation and infiltration
• Clinical presentation: +/- HTN, edema, microscopic-
hematuria; propensity for thromboembolic events
(particularly renal vein thrombosis)
Membranous Glomerulopathy

• Diagnosis made on kidney biopsy

– light microscopy shows glomerular capillary loops
that appear thickened without any proliferative
lesions. (ie nml cellularity)
– EM shows subepithelial electron-dense immune
complexes
– Immunofluorescence microscopy reveals a diffuse
granular pattern of immunoglobulin G (IgG) and C3
staining along the GBM; “lumpy bumpy” pattern in
the glomeruli as a result of autoantibodies to the
receptors on podocytes
Light Microscopy: MN
Electron Micrograph: MN
Membranous Glomerulopathy

• Tx for Idiopathic GN
– 1/3 of idiopathic MG remit
spontaneously in 6-12 months
– If does not remit-alternate
glucocorticoids with cyclophosphamide
or calcineurin inhibitors (tacrolimus or
cyclosporine)
Focal Segmental Glomerulosclerosis
• Predilection for black population
• Patients present with asymptomatic proteinuria or edema
and often times HTN and microscopic hematuria
• Diagnosis is made on renal biopsy-presence of segmental
scars in some glomeruli. EM shows visceral epithelial cell
foot process effacement but no immune deposits.
• Minority spontaneously remit
• Treatment for idiopathic FSGS: glucocorticoids or
calcineurin inhibitors (tacrolimus or cyclosporine)
Light Microscopy: FSGS
Minimal Change Glomerulopathy
(aka Minimal Change Disease)
• Most common cause of primary nephrotic syndrome in
children, but seen in adults too
• Pathogenesis thought to be related to production of
cytokines by immune cells that lead to podocyte dysfunction
• Clinical manifestations - acute onset of edema and weight
gain due to fluid retention, proteinuria, benign urine
sediment except few RBC’s
• Diagnosis confirmed with kidney bx which shows normal
glomeruli, tubules may show lipid accumulation, EMs show
a normal glomerular basement membrane with extensive
effacement of visceral epithelial foot processes.
• Treatment glucocorticoids
EM of MCG
General treatment for Nephrotic Syndrome
(idiopathic and secondary causes)
• Treat the consequences of nephrotic syndrome
– Hyperlipidemia with statins
– Edema with loop diuretics and low salt diet
– Anticoagulate if thrombosis occurs
Review of the secondary
causes of Nephrotic
Syndrome
 Systemic diseases associated
with Nephrotic syndrome
• Diabetic nephropathy • Drugs (FSGS, NSAIDS-
– Hyaline arteriosclerosis MG and MCG)
– Nodular • Infections (HIV-FSGS,
glomerulosclerosis with Hep B/C-MG, Mono –MCG)
Kimmelstiel-Wilson • Morbid obesity (FSGS)
lesion
– See next hidden slides • Reflux nephropathy
(FSGS)
• Amyloidosis
• Malignancies (MG,
– Congo red stain – apple MCG)
green
immunofluorescence • Thyroid disease (MG)
• SLE (MG)
 Evaluation for the secondary
causes of Nephrotic Syndrome

• Check for secondary causes related to systemic disease,

infection, malignancy, medication
– Ask about medication use (ie NSAIDS as in our patient)
– Test for DM
– Test ANA, dsDNA, C3 and C4 levels for autoimmune dz
– Check cryoglobulins, Hep B and C serologies, and HIV
testing for infectious causes
– serum free light chains and urine protein electrophoresis and
immunofixation
• Kidney bx for definitive dx
Treatment for secondary causes
of nephrotic syndrome
• Treat specific cause
– Remove offending agent (drugs ie NSAIDs)
– Treat DM
• glycemic control
• use ACEI/ARB
– Treat infection
– Treat other diseases as needed (MM, SLE, etc)
 Treat consequences of nephrotic
syndrome
• Hyperlipidemia with statins
• Edema with loop diuretics and low salt diet
• Anticoagulate if thrombosis occurs
 Case 7

Final diagnosis

Nephrotic syndrome
Probably from NSAID use
 Case # 8
• 10 year old girl complains of weakness, fatigue, fever
and a smoky colored urine.
• Past history reveals a recent episode of pharyngitis
three weeks ago which responded to antibiotics.
• Physical exam : Height is in the 50%ile, BP 132/62,
some periorbital edema is seen; pharynx is clear
• A urine analysis and kidney biopsy defines her lesion.
 Problem List

•10 year old girl

•Fever
•Smoky colored urine
•Past history of pharyngitis
•Periorbital edema
•Hypertension –is this hypertension for this 10 year
old female?
Pediatric Blood Pressure Normals
Patient is at 50% for height and is 10 year old. Her BP is 132/62.
Is the patient hypertensive?
 Thoughts Questions
• What do you think is going on? DDx?
– Nephritis vs nephrotic syndrome
• What other test would you like to order?
– Urine analysis
• Hematuria with red cell casts and mild proteinuria
• Does this finding help you focus your DDx?
– More likely nephritic due to the red cell casts.
What are the classic findings of
nephritic syndrome?
• Glomerular inflammation resulting in
– Hematuria - dysmorphic erythrocytes with or
without RBC casts
– Proteinuria-variable from fe hundred
milligrams to nephrotic range
– Leukocytes (leukocyturia) – presence variable
– Systemic findings - HTN, renal insufficiency,
mild edema and other systemic involvement*
 Glomerular Disease
Nephritic Syndrome
• Pathophysiologic mechanisms
– Immune complex deposition - granular deposits (low
complement levels except with IgA nephropathy)
• IgA nephropathy, IgA Vasculitis (HSP), Lupus Nephritis,
Infection related GN
– Anti-GBM antibodies - linear deposits (complement
level nml)
• Goodpasture’s syndrome
– Pauci- immune GN/small vessel vasculitis - few or no
immune deposits (complement level is normal)
• Wegener’s Granulomatosis, Churg Strauss Syndrome
 Glomerular Disease
Nephritic Syndrome
• Clinical Glomerulonephritis Syndromes based
on time course
– Acute GN
• ie infection related GN (ie due to strep infection)
– Rapidly progressive GN
• see next slide
– Chronic GN
• Lupus nephritis, IgA nephropathy
Clinical syndromes based on time course
Nephritic Syndrome
• Rapidly progressive GN
– Time course: Progression to renal failure in weeks
– Associated with any etiology of GN but particularly
common in patient with anti-GBM antibody disease
(Goodpasture’s syndrome) and pauci-immune small vessel
vasculitis (Wegener’s granulomatosis, Churg-Strauss)
– Definitive diagnosis made with kidney biopsy
– Treatment : high dose glucocorticoids, cyclophosphamide
(for pauci-immune), plasmapheresis (to remove circulating
antibodies in anti-GBM antibody dz)
Clinical syndromes based on time course
Nephritic Syndrome
• Chronic GN
– Time course: Slow progressive glomerular disease leading to end
stage disease in months or years
– i.e. Lupus nephritis, IgA nephropathy
• Acute GN
– i.e. Infection-related GN-appears either during or after infection
– (see next slides)
 Infection related GN
form of Acute GN
• Post streptococcal glomerulonephritis is now called infection
related glomerulonephritis b/c
1. Nonstreptococcal infections, particularly staphylococcus are more
common than strep infection (also seen with E coli and other gram neg
organisms)
2. GN can present at the time of infection rather than the delay of a week or
more.
• Shift in epidemiology of the disease –not just young, now affects
older and immunocompromised patients
• Sites of infection used to be from skin and respiratory tract, now
more wide spread
 Light microscopy
Infection related
Normal glomerulus glomerulonephritis

Increased Cellularity
(Neutrophils)
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Immunofluorescence micrograph shows granular staining

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 Nephritic Syndrome
Work up
• BMP (look for azotemia) • ANCA levels
• UA for protein and red cell • Anti-GBM levels
casts
• Serum C3 and C4 levels • ANA, Ds DNA
(complements) (lupus)
• ASO titer (if suspect strep • Serology for Hep B
infection) and C and HIV
– Rise in one week of initial
infection • Serum free light
– Peaks – 3-5 weeks chains and
– Returns to normal – 6 immunofixation
months to 1 year
 Back to the case
What is your working diagnosis?

Infection- related glomerulonephritis

 Nephritic vs Nephrotic
Acute nephritic syndrome Nephrotic syndrome
Protein 1+ <3.5 gms 4 + > 3.5 gms
Red cell casts 4+ 1+
Lipids 0 Fat droplets
Generalized edema 1 + 4+
 Case 8
Final diagnosis

Acute nephritic syndrome

Acute glomerulonephritis
Infection related GN
 Case # 9

• This 36 year old woman has noted persistent

urinary frequency and dysuria for the past
week and now develops a sudden onset of fever
and chills. She has also had nausea and one
episode of vomiting.

Thoughts?
What would you like to check on exam?
 Case # 9

• PE reveals a febrile, ill appearing patient with dry mucus

membranes, suprapubic tenderness and right
costovertebral angle tenderness.

What labs studies would you want?

• CBC showed leukocytosis
• BMP showed slightly elevated BUN
• Pregnancy test was positive
• A urinalysis showed many leukocytes with white cell casts.
• A urine culture and blood culture is pending.
 Problem List
• Urinary frequency
• Dysuria
• Fever and chills
• N/V and dehydration
• Right costovertebral pain (CVAT)
• Leukocytosis
• Azotemia
• Urine – white cells and casts
 Differential Diagnosis?
• Acute pyelonephritis
– Dysuria, fever, chills, nausea and vomiting, costovertebral
angle pain
– White blood cell casts
• Acute cystitis
– Dysuria, frequency, hematuria, pyuria
– Suprapubic pain
• Kidney stone
– Fever, CVAT
– But no hematuria seen in this patient
 Patient urine microscopy
What do you see?

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Describe the microscopic findings
of the renal biopsy slide.
 Thought questions
• What is the significance of the WBC
casts?
– Indicates intra-renal origin, not cystitis
What are some of the complications that
may develop?
– Chronic pyelonephritis
– Renal papillary necrosis (see next slide)
– Pyonephrosis
– Perinephric abscess
 Case 9

Final diagnosis

Acute pyelonephritis from Ecoli

infection