UNIVERSITY OF SANTO TOMAS

MPPRC Nephrology Case

General Data:
M.M. 24/F
Single, Roman Catholic, 3rd year medical student
Quezon City

CC: bipedal edema

History of present illness:

History started 4 days prior to admission when she noted that her feet up to her ankles were swollen
upon waking up. She described it as ill-fitting rubber slippers and shoes as it would leave marks on
her feet. It was not accompanied by any pain. She tried to massage her feet to relieve the symptoms
but did not help. During the interim she noted that the swelling reached up to her mid-calf and noted
that her skinny jeans became ill-fitting as well as it left sewing-pattern marks on her legs. She decided
to consult a general physician one day prior and was advised to drink Lasix 20mg/tab, 1 tab OD. She
was not seeing any improvement and noted that her thighs are now swollen too, limiting her
movement, hence consult and subsequent admission.

Review of systems:
She denied any weight loss. She recalls she had undocumented fever and sore throat 2 weeks prior.
She also denied any skin rashes, skin discoloration, eye discharge, hearing changes, changes in
smell or taste. She had no cough or colds, chest pain, palpitations, difficulty of breathing. There are
no noted changes in bowel movement, abdominal pain, nausea or vomiting. She has not experienced
any behavioral changes, seizure like episodes or body weakness but complained of intermittent
headache for the past 2 days.

Past Medical History:

She has no previous hospitalizations, surgical procedures, blood transfusion. She does not drink any
maintenance medications. She can’t recall her immunization status

Current Health Status:

She has a sedentary lifestyle. She does not drink alcoholic beverages but claims to occasionally
smoke flavored electronic cigarettes 2x a week for the past 2 years. She has no known allergies and
no known comorbidities.

Family History:
Her maternal grandfather died of myocardial infarction, and her paternal uncle died because of
recurrent urinary tract infection.

Physical Examination:
She was seen awake, conscious, coherent, pale-looking, wheelchair-borne and not in
cardiorespiratory distress. Her vital signs are as follows: BP 150/80mm Hg, HR 100 regular, RR 18,
Temp 36.7C. Her BMI is 20. She had pale palpebral conjunctivae, anicteric sclerae, no aural
discharge. There was a palpable 2x2cm soft, mobile submandibular lymphadenopathy bilaterally. The
buccal mucosa was dry, no noted oral lesions, the posterior pharyngeal wall was non-hyperemic.
There were no noted chest deformities, her AB was at the 5 th LICS MCL, precordium was adynamic,
no murmurs noted. She had symmetric chest expansion and bibasal crackles on auscultation. She
had flabby abdomen, normoactive bowel sounds, no hepatosplenomegaly. Her lower extremities was
swollen from the feet up to her mid-thigh with noted finger-marks when pressed on. She had difficulty
in moving her lower extremities hence manual muscle testing was not done. She had 5/5 MMT on her
upper extremities. Neuromuscular examination was not facilitated as the patient refused.

Learning Objectives:
1. Critique the data given to you. Are the data where they should belong?
2. Discuss your approach to the diagnosis.
a. correlate clinical symptoms to the pathophysiology
b. arrive at a plausible diagnosis
c. discuss possible pathologic findings, procedures and radiographs pertinent to the case
3. Create a concept map.
4. Discuss pharmacologic and non-pharmacologic management.

53. START (for the pathophysiology)

54 The slide shows the entirety of the pathogenesis of the disease. Boxes shaded in light blue are the pathophysiologic mechanisms,
grey for the subjective pertinent findings, yellow for the objective pertinent findings, red for the patient’s chief complaint, green for
the medical intervention provided, and purple for the possible laboratory findings.

55 We start first with the etiologic agent in our case. Streptococcus pyogenes, a Group A Streptococcus (GAS), which is the most
common cause of bacterial pharyngitis in children and adults. Transmission primarily occurs through direct human-to-human
contact, via respiratory droplets or nasal secretions from infected individuals.

So, along with pili and specific adhesion proteins, GAS adheres to the epithelial cells of the nasopharynx. The bacteria then releases
antigens and exotoxins which trigger the release of immune mediators, both in the innate and adaptive type of response.

Innate and adaptive immune responses are fundamental for defense against streptococcal pharyngitis and are central to the clinical
manifestations of PSGN

56 We first tackle the activation of the host’s innate response. Innate immune cells such as macrophages and neutrophils migrate to
sites of infection and help to destroy bacteria by secreting a number of soluble inflammatory mediators.

Stimulation of mononuclear cells causes the release of IL-6, which stimulates the hypothalamic temp control which caused the fever
(POA to the PVN)

Also, it will cause the release of TNF-alpha,

- which will facilitate WBC infiltration into the site of infection, causing release of endothelial mediators which increases the
gaps between the endothelial cells. This will then lead to leakage of proteins and fluid to the interstitial space causing the
PHARYNGEAL EDEMA/ erythema, and/or swelling. Moreover, it will increase the lymph drainage into the regional lymph
nodes causing the submandibular lymphadenopathy.
- AlsoTNF-alpha will facilitate a sophisticated process of killing the GAS which will cause the accumulation and deposition of
bacterial and cellular debris and inflammatory response which results into pharyngeal exudates present in pharyngitis

57 With the presence of the antigen upon bacterial invasion, The adaptive immune system is also activated with lymphocytes
responding to bacterial antigens. As GAS is cleared, there is subsequent production of antibodies against these antigenic
components formed or released in the course of streptococcal infection. This is An important factor in the development of kidney
dysfunction following a Streptococcal infection. The period between the resolution of pharyngitis and onset of nephritis is
compatible with the time required for the production of antibodies and the formation of immune complexes. As plasma cells
produce more and more antibodies, complexes can form which can then become deposited in the kidneys via the circulation.
58 To better understand the complications caused by immune complex deposition, we first briefly look at the structure and
functions of a healthy kidney. Here we can see the nephron which performs the normal filtration of waste products from the blood
in the kidney. These are composed of several structures including renal corpuscles which are responsible for filtering large amounts
of substances from the blood

59 The renal corpuscle consists of two main parts: the glomerulus which is a  a fine network of capillaries, and Bowman’s capsule.
The glomerular capillary membrane is similar to that of other capillaries except that it has three major layers, and each of the
component has a unique function, namely:
(1) endothelium which is fenestrated,
(2) basement membrane, which has a negative electrical charge and prevents the passage of plasma proteins 
(3) layer of epithelial cells known as podocytes which have long processes (foot processes) that wrap themselves around the
glomerular capillaries.  
Altogether, these form a highly efficient filtration system. 
We must also not confuse ourselves of the luminal side (red; capillary) and the interstitial side (yellow)

Fluid from the capillaries leaks into the Bowman’s capsule that surrounds the glomerulus. 
We also have the mesangium, which provides support through its phagocytic properties and removes materials that enter the
intercapillary spaces. Typically this area is narrow and contains only a small number of cells, however mesangial hyperplasia and
increased mesangial matrix occur in a number of glomerular diseases.

Now that we have an understanding of the anatomy of the renal corpuscle we can look more closely at how streptococcal antigen is
deposited in the kidney.

60 Going back
The kidney, considering its excretory function, and being a highly perfused organ, has the tendency to receive any substance which
enters/ is formed in the blood. “nephritogenic” proteins SpeB, a bacterial serine protease enzyme, and NAPIr, a secreted bacterial
protein known as “nephritis-associated plasmin receptor” are principal to PSGN and when present in the kidney precipitate
enzymatic damage its integrity causing the system becomes “leaky”. These bacterial antigens then bind and activate plasmin or
plasminogen which in turn activates the enzymes collagenase and metalloproteinases that degrade the basement membrane and
weaken endothelial cell tight-junctions. Disrupted membrane function allows bacterial antigens to be deposited inside the
Bowman’s space

61 then, there will be Immune complex formation and deposition

Immune complexes can be formed inside the Bowman’s space when free antibodies cross the disrupted basement membrane and
contact “planted” bacterial antigens already present, or alternatively, immune complexes that have formed in the bloodstream can
be trapped directly in the Bowman’s space.

62 this will then cause Complement activation in the kidney

Wherein the deposited complexes activates the classical complement pathway. A loss of plasma C3 levels correlates with
complement activation, and deposits of C3 proteins which can be detected through IF along the basement membrane and in the
Bowman’s space

63
Due to complement activation and generation of immunogenic factors, we then see an increased influx of immune cells. Deposits of
C3, antibody and bacterial antigens accumulate at the basement membrane near the podocyte foot processes, which is seen as
“humps”. Kidney function is severely hampered by influx of these cells that can block capillaries. As you can see in the image on the
right, There is also marked cell proliferation of mesangial and endothelial cells due to the presence of soluble inflammatory
molecules.

64 This, together with the immunologic damage to the renal basement membrane causes a spectrum of signs and symptoms
classical to PSGN.

65 . SO The immune cell recruitment and endocapillary proliferation causes hypoperfusion to the capillary loops, causing less blood
to be filtered. Upon laboratory exam, a decrease in GFR, Oliguria, and Azotemia may be seen. Also, hypoperfusion to the kidneys will
cause the activation or RAAS which will cause Na and water retention thereby expanding the extracellular fluid volume. This was the
one targeted by Furosemide. The expanded ECF volume is responsible for bipedal edema which is the patient’s chief complaint, and,
hypertension which caused the intermittent headache. This hydrostatic cause differentiates it from the primary cause of edema
caused by nephrotic syndrome which is oncotic in nature. Also, due to circulatory congestion, bibasal crackles was heard upon PE.
And the pale-looking appearance and pale-palpebral conjunctiva may be due to hemodilution causing anemia.

66. The immunologic damage to the renal corpuscles disrupts the glomerular permeability causing large molecules such as blood and
proteins to leak (proteinuria). As blood is permitted to pass into the urine, it may manifest as gross or microscopic hematuria. Upon
microscopy, dysmorphic RBCs may be seen due to mechanical and osmotic damage to its membrane. RBC casts on microscopy may
also be seen as RBC adheres to hyaline casts in tubular segments.

LASTly, Althogether, these manifestations of the patient can be classified as Nephritic syndrome, which is classical of PSGN--
emphasizing the three nephritic triads of it which are hematuria, Hypertension, and edema.