med school fool

[medschoolfool]

Bacteria and Diarrhoea

Clostridioides difficile infection is associated with yellow-white, patchy pseudomembranes on bowel mucosa. These pseudomembranes consist of neutrophil-predominant inflammatory infiltrate, fibrin, bacteria, and necrotic epithelium. Pts may develop non-obstructive colonic dilation known as toxic megacolon, which can lead to colonic perforation. It is an anaerobe, spore-forming, gram-positive rod.

Symptoms: diarrhoea, abdominal pain, and fever developed a colonic perforation.

Histologic findings: "acute inflammatory changes, epithelial necrosis, and a layer of denuded epithelium, fibrin, and inflammatory culls overlaying the mucosa”

Drugs that can alter intestinal flora and therefore cause C. diff infection: clindamycin, fluoroquinolones, and cephalosporins

Produces Toxin A (enterotoxin) and Toxin B (cytotoxin). Disrupt cellular cytoskeletons and intercellular tight junctions, leading to colonocyte apoptosis. Colonic mucosa responds to toxin exposure by forming yellow-white, patchy pseudomembranes.

Toxin A (enterotoxin):

Structure Active site at N-terminal domain (site of glycosylation) Central hydrophobic domain Binding site at C-terminal domain (binds to target surface)

Mechanism of action: binding to brush border of enterocytes → receptor-mediated endocytosis → change of conformation → exposure of active domain → glycosylation of target proteins (e.g., Rac, Cdc42, RhoA) → disruption of actin cytoskeleton functioning → increase in epithelial permeability and apoptosis → diarrhoea

Toxin B (cytotoxin):

Structure Binding site at C-terminal domain Translocation domain (required for pore formation) Cysteine protease-containing domain Catalytic domain

Mechanism of action: same as in toxin A, but can also cause pore formation within the endosomal membrane via insertion of the translocation domain → release of endosomal content into the cytosol → cytopathic effect

Campylobacter jejuni: watery diarrhoea that may become bloody, abdominal cramping, and fever. Neutrophilic infiltrate and crypt abscesses are identified on histology.

Salmonella typhi causes typhoid fever, which manifests with diarrhoea, abdominal pain, high fever, and salmon-coloured macules located mainly on the trunk. Histology demonstrates histiocytes, lymphoplasmacytic inflammatory infiltrate, and associated haemorrhage.

Shigella flexneri: sudden onset of severe abdominal cramping, bloody diarrhoea, vomiting, and high fever. Cryptitis, ulcerations, and crypt abscesses on histology.

Vibrio cholerae: cholera; sudden onset, voluminous, “rice water” diarrhoea and vomiting. Histology normal.

[medschoolfool]

Kinesin

Microtubule-associated, ATP-powered motor protein that facilitates anterograde transport of neurostransmitter-containing secretory vesicles down axons to synaptic terminals.

A targeted toxic insult to this protein would be expected to impair anterograde transport resulting in a deficiency of synaptic vesicles at the nerve terminal.

[medschoolfool]

Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (herniation of abdominal contents into the thorax) causes pulmonary hypoplasia from compression of the lungs. Neonates present with respiratory distress shortly after birth. X-ray findings include thoracic bowel loops; the distal end of a feeding tube may also be seen within the thorax.

Neonate with respiratory distress, asymmetric breath sounds, and a scaphoid abdomen; findings concerning for congenital diaphragmatic hernia.

Develops in 1st trimester due to incomplete fusion of pleuroperitoneal folds, which permits herniation of abdominal contents into the thoracic cavity. Compression of the developing lung causes pulmonary hypoplasia.

[medschoolfool]

Weber and Rinne Tests

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Insulin and Adrenergic Receptors

Alpha-2 adrenergic receptors inhibit insulin secretion

Beta-2 adrenergic receptors stimulate insulin secretion

The alpha-2-mediated inhibitory effect is generally predominant, causing sympathetic stimulation to lead to an overall inhibition of insulin secretion. However, if we were to block alpha-2 prior to catecholamine release/injection, then there would be an increase in insulin secretion because the beta-2 adrenergic receptors would only be open.

[medschoolfool]

QT Prolongation

Medications:

Macrolides: erythromycin, azithromycin

Fluoroquinolones

Antiemetics: ondansetron, metoclopramide

Azoles: fluconazole

Antipsychotics: haloperidol, risperidone

TCAs

Methadone

Class IA antiarrhythmics: quinidine

Class III antiarrhythmics: dofetilide

Congenital:

Romano-Ward syndrome (AD)

Jervell & Lange-Nielson syndrome (AR)

Congenital long QT syndrome is commonly caused by a mutation that slows the delayed rectifier potassium current that repolarises the cardiomyocyte action potential.

Excessive QT prolongation can trigger serious cardiac arrhythmia (ie, torsades de pointes), resulting in syncope or sudden cardiac death.

[medschoolfool]

Angioedema

Angioedema with pruritus and urticaria is caused by mast cell activation (type I hypersensitivity). Opioids can directly activate mast cells.

Angioedema without pruritus and urticaria is due to excess bradykinin. ACE inhibitors and C1 inhibitor deficiency can cause excess bradykinin.

Angioedema is a rare and serious adverse effect of ACE inhibitor therapy. ACE inhibition increases bradykinin levels, which increase vascular permeability and lead to angioedema. Symptoms include tongue, lips, or eyelid swelling and, less frequently, laryngeal oedema and difficulty breathing. ACE inhibitors should be discontinued in affected patients.

ARBs do not cause excess bradykinin.

[medschoolfool]

Panic Disorder

Consists of recurrent and unexpected panic attacks characterised by an abrupt surge of anxiety and distressing cardiopulmonary/neurologic symptoms.

Agoraphobia, a common comorbid disorder, results in anxiety about and avoidance of situations where patients may feel trapped and helpless in the event of a panic attack (eg, crowds, enclosed spaces, public transportation).

Requirements:

Recurrent and unexpected panic attacks with 4 or more of the following:

Chest pain, palpitations, SOB, choking

Trembling, sweating, nausea, chills

Dizziness, paresthesia

Derealisation, depersonalisation

Fear of losing control/dying

Those with panic disorder tend to worry about additional attacks, which can lead to avoidant behaviours.

Treatment: SSRI/SNRI + CBT

Acute treatment: benzodiazepines