Pathophysiology of generalized

edema and protein losing-

nephropathies

How to approach a patient with

generalized edema?

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Case summary
 Patient Profile
31 year old women, housekeeper, lives with her husband in
Bangkok.
last menstrual period 15 October 2023, P0 (never had a kid).

Cheif Complaint
Lower extremity edema for 2 weeks PTA

Present Illness
1. 1 month PTA: She had periorbital edema.
2. 10 days PTA: exhaustion while doing routinely work.
3. 2 week PTA: lower extremity edema, muscle and joint pains.
4. Continuous feeling of tiredness and fatigue; unable to go to work, required
assistance to come to the hospital.
Past history
Diagnose with SLE 3 years ago, which have led to acute serositis and
musculoskeletal pains

Family and social history

Married, no children

Drug history
400mg ibuprofen for joint pain; for 3 months
Currently on: prednisolone, hydroxychloroquine, azathioprine
Oral contraceptive pills
Multivitamins
Physical examination
Vital Sign General apperance
Body Temp. 37.8 Thai female
RR: 24 times per min Alert
HR: 92 BPM Ｍ ild distress
BP: 150/90 mm Hg Generalized edema; puffy eyelid
Mild pallor
HEENT No jaundice
Body weight: 60kg (gain 5 kg in 2 wks)
Periorbital edema
height: 160 cm
Mildly pale conjunctiva
Malar rash
Oral ulcer on tongue
Heart
Normal S1, S2, regular rhythm, no murmurs or gallops

Chest
Decrease breath sound at both lower lungs, plus dullness on percussion

Abdominal Extremities
Mild distention Pitting edema 3+ of lower legs
Active bowel sound Skin
No hepatomegaly No petechiae
Soft, not tender
Shifting dullness on percussion CNS
Within normal limits
Pertinent Subjective Data
Pertinent Objective Data
 Peritent Subjective Data
31-year-old Thai woman and living in Bangkok
Housekeeper
Last menstrual period (LMP) 15 October 2023
Parity 0 (P0)
Periorbital edema (1 month PTA)
Lower extremity edema and sometimes muscle and joint pains (2 weeks PTA)
Felt tired (10 days PTA)
This morning more tired and fatigue.
diagnosed of systemic lupus erythematosus (SLE) 3 years ago
400-mg ibuprofen each day for joint pain for three months.
prednisolone, hydroxychloroquine, and azathioprine, in addition to oral
contraceptive pills and a multivitamin.
 Pertinent Objective Data
RR: hyperventilation (24 times per minute)
HR: slightly high (92 bpm)
BP: high (150/90 mm Hg)
Mid acute distress
Puffy eyelids
Weight gain 5 kg in 2 weeks
Periorbital edema
Malar rash (HEENT)
Mildly pale conjunctiva (HEENT)
Oral ulcer on tongue (HEENT)
Decreased in breath sound at both lower lung
Dullness on percussion (Chest)
Mild distention, active bowel sound (Abdomen)
Shifting dullness on percussion (Abdomen)
Pitting edema 3+ of lower legs
Normal S1, S2, regular rhythm, no murmurs or gallops (Heart)
 Problem List

Edema at lower extremities

Subjective
31-year-old Thai woman and living in Bangkok
Periorbital edema (1 month PTA)
Lower extremity edema and sometimes muscle and joint
pains (2 weeks PTA)
Felt tired (10 days PTA) and more tired and fatigue this
morning
Diagnosed of systemic lupus erythematosus (SLE) 3 years
ago
400-mg ibuprofen each day for joint pain for three months.
Prednisolone, hydroxychloroquine, and azathioprine,
Oral contraceptive pills and multivitamins
Objective
RR: hyperventilation (24 times per minute)
HR: slightly high (92 bpm)
BP: high (150/90 mm Hg) hypertension
Mid acute distress
Puffy eyelids
Weight gain 5 kg in 2 weeks
Periorbital edema
Malar rash (HEENT)
Mildly pale conjunctiva (HEENT)
Oral ulcer on tongue (HEENT)
Decreased in breath sound at both lower lung
Dullness on percussion (Chest)
Mild distention, active bowel sound (Abdomen)
Shifting dullness on percussion (Abdomen)
Pitting edema 3+ of lower legs
Normal S1, S2, regular rhythm, no murmurs or gallops (Heart)
Assessment
Nephrotic Syndrome
SLE-induced nephrotic syndrome (immune complex, hypersensitivity
type III)
NSAID-induce nephrotic syndrome
Nephritic Syndromes
Lupus nephritis (immune complex, hypersensitivity type III)

Indicative of nephrotic: > 3.5 gm/day proteinuria, hypoalbuminemia,

hyperlipidemia, lipiduria, edema
Indicative of nephritic: hypertension, microscopic hematuria, azotemia,
variable proteinuria, oliguria, edema
Lab investigation
Urine protein: very high Liver function
Lipid profile Albumin: 2.1 (low)
LDL-C: very high ALT and AST: slightly low
Serology test Blood chem
dsDNA: high BUN: 25 (slightly high)
C3: low GFR: 101 (slightly high)
C4: low CBC:
Urine analysis WBC low
Foamy, slightly turbid RBC: low
Sp. Gr.: high Hct: low
Protein: 3+ Hb: low
Blood: Trace
RBC: 3-5 (high)
Fatty cast
Oval fat body
Pathophysiology of generalized
edema and protein losing-
nephropathies
Guyton and hall textbook of medical physiology 14th
 (1)

(2)
How to approach a patient with
generalized edema?

History taking
Physical examination
Lab investigation
HISTORY TAKING
OPQQRST
O – Onset & chronology The timing of the edema
P - Position & radiation Changes with position
Q – Quality Location
Q – Quantification Medication history
R – Related symptom Assessment for systemic
S – Setting diseases
T – Transforming factors

https://www.aafp.org/pubs/afp/issues/2022/1100/peripheral-edema.html
 EDEMA
Acute (<72 hr.) Chronic (>72 hr.)
: Localize : Generalize

Deep venous thrombosis (DVT) Congestive heart failure (CHF)

Ruptured popliteal cyst Renal disease
Acute compartment syndrome Hepatic disease
from trauma
Recent initiation of calcium
channel blockers
 https://www.researchgate.net/publication/320081580_Approach_to_leg_Edema/fulltext/5a320905aca27271441f18bd/Approach-to-leg-Edema.pdf?
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Physical examination and Lab investigation

OVERVIEW Approach to
Generalized edema

CHECK JVP
JVP NORMAL JVP ELEVATED

Chest Radiography
Check :
Serum albumin Normal Heart size
Cardiomegaly
Urine protein

Normal Serum albumin Decreased Serum albumin Check: Lung

Check Echo
Fields

Abnormal Urine Pericardial Effusion Poor Contraction Pulmonary

Normal Urine analysis Clear Lung Fields
sediment Hypertension
Pattern
Pericarditis Congestion Heart
Check : Thyroid Check : BUN / /Temponade Failure Evaluate for
Function Test(TFTs) Creatinine (CHF) Evaluate for Cor-
Pericardial
pulmonale
Constriction

Evaluated for Renal Normal

Proteinuria
Pathology Urinalysis

Decrease TFTs Check :

Normal TFTs Decrease
24-hrs Urine
Check: Check : Pre-albumin Cholesterol
Protein Normal LFTs
LFTs Cholesterol Prealbumin
Myxedema < 20 mg/dl
Ideopathic
edema > 3.5 g Protein < 3.5 g Protein
Normal Cholesterol
Abnormal LFTs Malnutrition Prealbumin
Drug-induced Edema > 20 mg/dl
e.g : Minoxidill, Nephrotic Capillary Abnormal Protein losing
Fludrocortizine,Diazoxi Syndrome leak protein enteropathy
Evaluate for Liver pathology eg:
de, ect. syndrome synthesis
Cirrhosis
 Approach to
Generalized
edema

CHECK JVP
JVP NORMAL JVP ELEVATED

Check :
Serum albumin
Urine protein

Normal Serum Decreased

albumin Serum albumin https://www.researchgate.net/publication/320081580_Approach_to_leg_Edema/fulltext/5a320905aca27271441f18bd/Approach-to-leg-Edema.pdf?
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 Normal Serum
albumin

Normal Urine Abnormal Urine

analysis sediment

Check : Thyroid Check : BUN /

Function Test (TFTs) Creatinine

Normal TFTs Decrease TFTs Evaluated for Renal

Pathology
Drug-induced Edema
Ideopathic
e.g : Minoxidill, Myxedema
edema
Fludrocortizone,
Diazoxide, ect. https://www.researchgate.net/publication/320081580_Approach_to_leg_Edema/fulltext/5a320905aca27271441f18bd/Approach-to-leg-Edema.pdf?
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 https://www.researchgate.net/publication/320081580_Approach_to_leg_Edema/fulltext/5a320905aca27271441f18bd/Approach-to-leg-Edema.pdf?
origin=figuresDialog_download&_rtd=e30%3D&_tp=eyJjb250ZXh0Ijp7ImZpcnN0UGFnZSI6Il9kaXJlY3QiLCJwYWdlIjoicHVibGljYXRpb24ifX0

Decreased Serum
albumin

Check : Decrease
Prteinuria Normal Normal Cholesterol
Urinalysis Prealbumin
LFTs Prealbumin
Check : Cholesterol < 20 mg/dl
24-hrs Urine
Protein Check Normal
Cholesterol Protein losing
: LFTs
Prealbumin enteropathy
> 3.5 g < 3.5 g > 20 mg/dl
Protein Protein Abnormal Abnormal
LFTs Malnutrition
protein
synthesis
Nephrotic Evaluate for Liver Capillary
Syndrome pathology eg: leak
Cirrhosis syndrome
 Generalized
edema
CHECK JVP JVP ELEVATED

Chest
Radiography
Cardiomegaly Normal Heart size

Check Echo Check: Lung

Fields

Pericardial Poor Pulmonary Clear Lung Fields

Effusion Contraction Hypertension Pattern

Pericarditis / Congestion Heart Evaluate for Evaluate for

Temponade Failure Cor-pulmonale Pericardial
(CHF) Constriction
https://www.researchgate.net/publication/320081580_Approach_to_leg_Edema/fulltext/5a320905aca27271441f18bd/Approach-to-leg-Edema.pdf?
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References
Complement C3 and C4 - South Tees Hospitals NHS Foundation Trust. (2022, April 27). South Tees Hospitals NHS Foundation Trust.
https://www.southtees.nhs.uk/services/pathology/tests/complement-c3-and-c4/#:~:text=Interpretation,cryoglobulinaemia%20or%20C1%2Dinhibitor%20deficiency.
Complement C3 (Blood) - Health Encyclopedia - University of Rochester Medical Center. (n.d.). https://www.urmc.rochester.edu/encyclopedia/content.aspx?
contenttypeid=167&contentid=complement_c3_blood#:~:text=The%20normal%20range%20for%20a,lupus%2C%20levels%20usually%20go%20down.
Glomerular filtration Rate (GFR). (n.d.). https://www.healthcare.uiowa.edu/path_handbook/Appendix/Chem/GFR.html
Lupus blood test results: What to know | HSS Rheumatology. (n.d.). Hospital for Special Surgery. https://www.hss.edu/conditions_understanding-laboratory-tests-and-results-
for-systemic-lupus-erythematosus.asp#:~:text=Low%20C3%20and%20C4%20levels,autoimmune%20hemolytic%20anemia%2C%20AIHA).
Rekvig, O. P. (2019). The DSDNA, Anti-DSDNA Antibody, and lupus nephritis: what we agree on, what must be done, and what the best strategy forward could be. Frontiers in
Immunology, 10. https://doi.org/10.3389/fimmu.2019.01104
Mechanisms of kidney injury in lupus nephritis – the role of anti-dsdna antibodies. (n.d.). PubMed Central (PMC).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569852/#:~:text=Accumulating%20evidence%20suggests%20that%20in,materials%2C%20respectively%2C%20to%20resident%2
0renal
Admin, & Admin. (2021, November 24). Nephrotic Syndrome: pathogenesis and clinical findings | Calgary Guide. The Calgary Guide to Understanding Disease.
https://calgaryguide.ucalgary.ca/nephrotic-syndrome-pathogenesis-and-clinical-findings/
 OLIVIA WILSON
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