Peculiar pattern of pulmonary edema

Usually, left-sided cardiac pathology causes bilateral pulmonary edema but still, the unilateral pattern is seen in a fair number of cases, usually involving right lung parenchyma.

Likely mechanisms include:

1) Lymphatic drainage on the right side is via low caliber right bronchomediastinal trunk as opposed to the more robust thoracic duct on the left side.

2) Numerous conditions ranging from hypertension to valvular pathology can cause enlargement of the left side of the heart.

This will preferentially impinge on the left pulmonary artery causing reduced capillary perfusion and ultimately congestion of left lung parenchyma.

3) In cases of mitral regurgitation jet of regurgitating can preferentially impact either of the right or left pulmonary veins, hence explaining more profound edema on either side.

So, if according to the patient's history and clinical examination suspicion of cardiac failure remains high, then immediate intervention with diuretics and nitrates is warranted in spite of a unilateral pattern of pulmonary edema.

Kirtan Patolia

Obesity in Prader-Willi syndrome and WAGR syndrome

The delicate balance between food consumption and energy expenditure involves the modulation of orexigenic and anorexigenic signals at the hypothalamus.

OREXIGENIC PATHWAY- It involves peripheral mediators like ghrelin and neuropeptide-Y. 

They act on NPY-AgRP(neuropeptide-Y and agouti-related peptide) neurons which subsequently mediates orexigenic signals via second-order neurons that release peptides like orexin at the hypothalamus.

ANOREXIGENIC PATHWAY- It involves peripheral mediators like leptin, amylin, and PYY(Peptide YY).

They act on POMC/CART(Pro-opio melanocortin/Cocaine and amphetamine-regulated transcript) neurons.

These neurons release an alpha-melanocyte-stimulating hormone which in turn stimulates second-order neurons that release TRH, CRH and hence mediate catabolism.

They also simultaneously inhibit the anabolic pathway.

Now back to the pathogenesis of obesity in these syndromes.

In Prader-Willi syndrome levels of PYY are low due to loss of imprinted genes on chromosome 15q11-q13.

This results in reduced catabolism and enhanced uninhibited anabolism.

It is not uncommon for such patients to have BMI above 40.

In WAGR syndrome there is haploinsufficiency of BDNF(Brain-derived neurotrophic factor).

Alpha melanocyte-stimulating hormone in the catabolic pathway acts through melanocortin receptors(MC4R) on second-order neurons.

Downstream signaling pathways of MC4R involve BDNF hence explaining obesity in these patients.

In fact, efforts are already underway to reduce PPY levels and modulate BDNF to control obesity in these disorders.

Kirtan Patolia

Paroxysmal nocturnal hemoglobinuria

1)PNH originates from an acquired mutation ( frame-shift that creates a premature stop codon) in a myeloid stem cell, the acquired mutation in PNH occurs in the PIGA gene which is responsible for the first step in the synthesis of the GPI anchor that attaches CD55 and CD59 to the cell surface.

2)Complement detects self vs nonself cells by these complement inhibitors. Function of these complement inhibitors is to:

3)In the absence of these inhibitors, complement proteins bind cell membranes of our own cells and through the alternative complement pathway can lyse self-cells.

4)CD55/DAF decrease → More C3 convertase→Increase C3b→Increase opsonization→Extra Vascular Hemolysis.

   CD59/MIRL decrease→More MAC→Intra Vascular Hemolysis.


5)Why nocturnal hemoglobinuria- hemolysis occurs throughout day but its more at night because:   (a)Increased hemolysis in night due to respiratory acidosis(Shallow breathing).
 (b)Overnight concentration of urine is more and hemoglobinuria is clearly evident.

6)Diagnosis:(a)Flow cytometry- decrease CD55 and CD59 levels.
                     (b)HAM test-confirmatory.
                     (c)Direct coombs test-Negative (Helps to differentiate PNH and AIHA- its positive in AIHA)                                                                           

7)Treatment: 

(a)Ravulizumab- long acting C5 complement inhibitor

(b)Eculizumab- It is an Antibody to C5 and prevents its clevage to C5a and C5b, so no MAC. Ravulizumab has a half life that is three to four times longer than eculizumab.

-Srikar Sama

SOURCE: UpToDate, Uworld.

Psammoma Body

Psammoma body :

1)Psammoma bodies are round microscopic calcific collections.

2)A single necrotic cell act as a nidus and calcium deposits around it in laminated and concentric fashion.Psammoma body is an example for dystrophic calcification (Ca2+ deposition in abnormal tissues secondary to injury/necrosis in context of Normal calcium levels).

3)It is used in histopathology for diagnosis of certain tumours like:

Mnemonic : Remember it as SPAMmoma

          S- Serous cystadenocarcinoma of ovary

              Somatostatinoma


        PA-Papillary thyroid carcinoma

              Papillary renal cell carcinoma

       M- Mesothelioma

             Meningioma.

-Srikar Sama

Atrial myxomas

Myxomas are the most common primary cardiac neoplasm. 90% occur in the atria (mostly left atrium). The cells originate from a multipotent mesenchyme that is capable of neural and endothelial differentiation. Myxomas produce vascular endothelial growth factor (VEGF), which probably contributes to the induction of angiogenesis and the early stages of tumor growth.

GROSS FEATURES :Typical myxomas are pedunculated, the surface may be smooth, villous or friable.

HISTOLOGY : Gelatinous material, myxoma cells immersed in glycosaminoglycan. 

CLINICAL MANIFESTATIONS : 

1)Obstruction : Myxomas are usually described as "ball valve" obstruction of AV valves which may cause syncopal episodes, Dyspnea.

2)Influenced by position : Upright position may exacerbate the condition whereas lying down may decrease it.

3)Embolization : If the myxomas are friable or villous, fragments of mass can detach and present with systemic emboli.

4)Constitutional symptoms (eg: fever, weight loss) : Some myxomas release cytokines like IL6 which may produce constitutional symptoms.

5)Auscultation may reveal early diastolic "tumor plop".

TREATMENT : Prompt resection is required because of the risk of embolization or cardiovascular complications, including sudden death.

-Srikar Sama

Dietary Risk Factors For Calcium Stones

1) Fluids:
A lower fluid intake will lead to lower urine output, thereby promoting stone formation by increasing the concentration of calcium and oxalate.

Warfarin Induced Skin Necrosis

Warfarin-induced skin necrosis is a complication of warfarin therapy in which the patient develops demarcated areas of purpura and necrosis of skin including the extremities, breasts, trunk, or penis.

Mechanism:
1)Mechanism of action of Warfarin is it inhibits VitK epoxide reductase,so there is decrease in synthesis of VitK dependent factors - (factors II, VII, IX, and X) and natural anticoagulants (protein S and protein C).


2)Now no new clotting factors are produced but the old circulating clotting factors are still present (warfarin has no effect on already circulating clotting factors).


3)Among the factors II, VII, IX, X, ProteinC that are already present,ProteinC has the shortest half life,So ProteinC is depleted more rapidly than the others.


4)Now there is no anticoagulant in the body to oppose the action of already present clotting factors,so there will be initial coagulation till factors II, VII, IX, X gets depleted i.e till their half lives are completed.


5)This initial coagulation occurs in dermal vasculature which causes Skin Necrosis.

Prevention:
Overlapping of warfarin with heparin during the first several days of warfarin administration(if Heparin is given along with warfarin, this prevents functioning of circulating factors since heparin inhibits the activity of circulating thrombin and factorXa) and then warfarin is continued for long term therapy.


Source: UpToDate, First Aid.

-Srikar Sama

New application process for ECFMG registration

Hello,

This post is regarding new application process for ecfmg registration.


STEP1 : The process for obtaining USMLE ID is still the same which has been described very clearly here http://www.medicowesome.com/2016/12/how-to-apply-for-usmle-exams.html#more


STEP2 - ECFMG CERTIFICATION USING IWA:

1)when you go to IWA and login to your account you will only have one option : apply for certification (no application for examination any more ) so you will just click on that.

2)simply follow the steps and confirm you information and you will end up getting a payment page of 125$.


STEP3 - FORM 186 :

1)After payment they will send you form 186 (unlike before you dont need to go to your medical school and have it signed by your deen)

2)You will simply go to the website :- https://www.notarycam.com/ecfmg/


STEP4 - INTERVIEW WITH ONLINE NOTARY :

1)Fill an application and upload form (186) and high quality image of your passport or photo ID preferably but not necessarily in english.

2)You will receive an email from one of the online notaries and schedule an appointment of an online meeting with him/her.

3)If you are ready at the moment you can schedule an appointment immediately(which is what i did) or you can schedule for an appointment later.

4)During your meeting with the notary please prepare your passport as you will be asked to show it, to confirm your identity.

5)Afterwards the notary will ask you to position your self to the mid of screen and ask your permission for taking a screenshot.(If your webcam is of low quality they will ask you to mail them a passport picture of yours,so be ready with that too)

6)Then you will have to electronically sign your form-no need to actually sign it,they will display your name in few fonts and you have select one.

7)Now you have done your part.The notary will seal the document and send it to the ecfmg.

8)You will get an 2 emails after this process-one from notary that they have sent your form186 to ECFMG and second email is from ECFMG which you will be getting after few days that they have accepted your form 186.

-Srikar Sama

A rare type of fistula-Arterioenteric fistula

As the name suggests, this type of fistula is characterized by an anomalous connection between the bowel and arterial lumen.

CAUSES- Diverticulitis, Inflammatory bowel disease, bowel wall perforation, penetrating ulcers, aneurysms, prosthetic vascular grafts, radiation, trauma, or foreign body ingestion.

CLINICAL PRESENTATION- Depending on the cause it could include abdominal pain, hematochezia, hematuria (say if diverticulitis perforates bladder wall), sepsis, syncope (due to volume depletion from major bleed), gangrenous involvement of limbs due to vascular insufficiency, etc...

MANAGEMENT- Prompt diagnosis with laparoscopic intervention to eliminate fistula and any revascularization procedures if needed is the key to reduce mortality in such patients.

Kirtan Patolia

A few USPSTF guidelines

Hello,

USPSTF guidelines are important to remember for step 2 CK, step 3 and residency!

Here are a few high yield ones!

Ingenious Immune System

Hello friends, today let's take a moment to appreciate how amazing is our immune system.

In our immune system, just like any regular car, there are brakes in place to regulate its working. Removing brakes can certainly enhance its function which underlies the concept of immune checkpoint blockade.

Two such molecules on the surface of T-cells are CTLA-4(Cytotoxic T-lymphocyte associated protein 4) and PD-1(Programmed cell death protein 1).

When CTLA-4 binds to its ligands B7-1 and B7-2 which are often expressed in increased numbers on tumor cells it results in inhibition of T-cells and hence allowing tumor cells to evade apoptosis and survive.

Similarly when PD-1 binds to PD-L1on tumor cells inhibitory signals are relayed to T-cells.

In macrophages signal, regulatory protein alpha mediates inhibitory signals on interacting with CD47 on tumor cells.

In NK-cells KIR2DL1(killer cell immunoglobulin-like receptor 2DL1) mediates inhibitory signals.

So blocking these inhibitory signals by monoclonal antibodies can remove "brakes" on the immune system ultimately enhancing their ability to kill tumor cells.

Approved antibodies include:

Anti CTLA-4-Ipilimumab

Anti PD-1-Nivolumab, Pembrolizumab

Anti PD-L1-Avelumab,Durvalumab

Kirtan Patolia

Authors' diary: 53 facts about me

Another vlog before my long weekend ends =)

Pemphigus vulgaris vs Paraneoplastic Pemphigus vulgaris (PNP)

Hello friends, today let's talk about subtle differences between pemphigus Vulgaris and Paraneoplastic Pemphigus Vulgaris

1. SITE OF INVOLVEMENT

Pemphigus Vulgaris usually involves buccal and labial mucosa.

PNP causes severe stomatitis as well as targetoid lesions on palms and soles much like erythema multiforme.

2. ANTIBODIES INVOLVED

In Pemphigus Vulgaris antibodies are directed against intercellular adhesion molecules desmoglein-1 and desmoglein-3.

However, in PNP apart from desmoglein-1 and desmoglein-3 antibodies are also directed against envoplakin, plectin, desmoplakin, periplakin, and BPAG-1. 

3. IMMUNOFLUORESCENT PATTERN

In Pemphigus Vulgaris typical chicken-wire pattern is seen due to the intercellular deposition of IgG and C3

In PNP, that is not the case as although there is IgG deposition in all layers but not intercellularly and furthermore C3 is deposited along basement membrane as in Bullous pemphigoid.

4. VISCERAL INVOLVEMENT

In Pemphigus Vulgaris it is rare while in PNP often mucosa of the esophagus, stomach, duodenum, intestines, and the pulmonary epithelium is seen.

Prognosis is quite poor in PNP with bronchiolitis obliterans and sepsis being chief complications.

Mostly seen in Non- Hodgkin's lymphoma and CLL.

- Kirtan Patolia