Myotonic dystrophy - MC adult dystrophy, AD
Triplet repeat dz – repetition of tri-nt’s (there are 4 dz’s with this abnormality – HD, Fragile X – have macrorchidism (big testes in adolescents), Friedrich’s ataxia, Myotonic dystrophy).
In future generations, dz gets worse – anticipation. Therefore, can anticipate that in future dz’s it will get worse. For each generation, there are more triplet repeats added on, leading to a more defective protein and the dz gets worse and worse.
Example: genetic counselor telling couple that they have a dz, where if are to have children, the dz will be fatal in their children. The couple didn’t listen to their counseler, had a child and the child died only after 1 month. What was it and what is this: an ie triplet repeat disorder (anticipation) Muscle weakness in face (so mouth is drooped open).
50. Myotonic dystrophy
Example: pt with failure to release grip on golf stick (or when shaking hand) – they cannot relax their muscle grip, diabetes, cardiac abnormality
Myasthenia Gravis
AutoAb against Ach receptor – it’s an IgG Ab, therefore is an Example: of type II HPY, like Grave’s, which is an IgG Ab against the receptor (by definition, this makes it type II). Whether you destroy the receptor or just block it is irrelevant. Ach cannot hook into it and therefore there is muscle weekness. The first muscles are the lids, which leads to lid lag. They also get double vision bc muscles of the eye are messed up, leading to diplopia. Eventually, they get dysphagia for solids and liquids (gets stuck in upper esophagus, bc this is where there is STRIATED muscle). Eventually muscle dz prevails throughout.
Feel energized in the morning and feel tired at night. Tensilon test positive. Can die. Rx is acetylcholinestrase inhibitors. By giving an inhibitor, block the breakdown of Ach and build up Ach. With few receptors you have in there, there is a larger chance of hooking up to the receptors and pt does well. However, eventually, no receptors there and it doesn’t matter how much Ach is there, so pt is screwed. Then, her only option is a thymectomy.
The thymus is in the anterior mediastimun. Trick question: they can ask, what is the pathology? They can describe MG and ask, what do you expect to see in the
mediastinum? Do NOT put thymoma. This is a malignancy of the thymus and does occur in 15-20% of cases, but isn’t the MC pathology seen in the thymus in a pt with MG. See germinal follicles in the thymus (remember, this T cell country, not B cell country, so its abnormal to have germinal follicles here) – they are the ones making the Ab causing the MG. So, by doing a thymectomy for Rx, you are removing the Ab
producing tissue. 1/3 pts get a complete cure. 1/3 get a partial cure, and 1/3 die bc they waited too long for thymectomy and Rx and didn’t have receptors, anyway. So, B cell hyperplasia is the MC thing you see, not thymoma. This where the Ab is being made.
Lupus
Butterfly distribution on the face (malar rash)
Of all the autoimmune dz’s this one is the most likely one to have a “+” ANA (99% sensitivity). The Ab’s you want to order to prove that its lupus are anti-Smith Ab (which has a 100% spec, therefore no false pos – therefore 100% PPV) for lupus, meaning that if you test “+” for this Ab, you have Lupus. The other Ab is anti –dsDNA – this not only indicates that you have lupus, but also that you have KIDNEY dz. That has a 98% spec, too. So, these are two good Ab’s to confirm lupus. Morning stiffness is present in lupus (simulates Rh arthritis/photophobia), rash, pericarditis; LE cell prep – Anti – DNA Ab’s are phagocytosed by neutrophils, and they have altered DNA. Not specific for lupus (waste of time).
29. Pericardial fluid
Note the LE cell in the center of the slide, LE cells are altered DNA phagocytosed by a neutrophil, pericarditis/effusion is the most common cardiac manifestation of SLE
30. SLE: malar rash
Progressive Systemic Sclerosis/CREST
Tight face, telangiectasia, Raynauds, dysphagia (solids and liquids), dystrophic
calcification, sclerodactly; if kidneys involved, it is progressive systemic sclerosis, NOT CREST (doesn’t involved kidneys).
Dermatomyositis
Racoon eyes, elevated serum CK, rash over the PIP (goutren’ patches), highest assoc with underlying cancer.
37. Dermatomyositis
Sjogrens syndrome
Assoc with rh arthritis, autoimmune – Ab’s destroy salivary glands leading to dry mouth, lacrimal glands leading to dry eyes.
Example: bx of lower lip which is a confirmatory test – its looking to see if there is destruction of the minor salivary glands – see lymphocytes (which is confirmatory dx). Ab’s are anti-SSa (aka anti-Ro) and anti-SSb (aka anti-La) (SS = Sjogren’s syndrome). Anti-ro can also be in lupus pts, and can cross the placenta and disrupts the baby’s conduction system (leads to complete heart block).
Skin
Basal cell carcinoma (upper lip) Squamous cell carcinoma (lower lip)
Psoriasis – silvery lesion that is red and raised. Can involve the hands, scalp – pts think they have dandruff (aka seborreic dermatitis – from malasezia furfura), but they really have psoriasis. On black person won’t see red lesion, will see silver one. Rash at pressure points – esp the elbow.
19. Psoriasis:
Note the raised red plaque with silvery scales on the surface. Pinpoint bleeding will occur if the scale is picked off (Auspitz sign). (Drm019)
20. Nail pitting in a patient with psoriasis
21. Histologic section of psoriasis:
Note the hyperkeratotic surface, which corresponds to the silvery scales on the skin in the lesion above. There is acanthosis and accentuation of rete ridges into the dermis. Note how close the superficial dermis comes to the surface of the scale.
Atopic dermatitis – child with allergic diathesis starts dz; have eczema (aka atopic dermatitis); type I HPY.
3. Atopic dermatitis in child: Family history of IgE-mediated disease is common (Drm003)
Contact dermatitis – ie to metal (nickel); type IV HPY
Example: pathophys is equalant to what? “+” PPD, bc both are type IV HPY
4. Contact dermatitis to nickel: Note the eczematous rash; this is type IV hypersensitivity (Drm004)
Seborrheic Dermatitis
Due to Malassezia furfur (a fungus) IC pt (ie AIDs)
This is a preAIDs lesion
5. Seborrheic dermatitis (dandruff): This is due to M. furfur (Drm005)
Tinea capitis
Example: pt with bald spot on head, fluouresces and seen with black light blacklight (UV-A light)
Can cause Tinea capitis (now Trichophyton tonsurans is MCC)
Bc the fungus involves the inner portion of the shaft, there are no fluorescent metabolites, and is Wood light negative
6. Tinea capitis with a positive Wood's lamp: Microsporum canis infects the outer part of the hair shaft, hence the fluorescence. T. tonsurans is the most common cause of tinea capitis and does not fluoresce (Drm006)
All the other superficial dermatophyte infections including Tinea corporis (ring worm) Example: red outer edge and clear center, what is first step in workup? Scrape outside and do KOH prep, and see hyphae and yeast forms. All other superficial
dermatophyte infections (except Tinea capitis) are due to trychophyton rubra. What is the color around Tinea capitis? Red (= rubra) (how to remember it).
7. Tinea corporis ("ringworm"): Note the outer red border and clear center. T. rubrum is the most common cause. (Drm007)
8. KOH preparation of above lesion: Note the hyphae and yeast forms (Drm008)
9. Tinea versicolor:
Note the areas of pigmentation and depigmentation. It is due to M. furfur. (Drm009)
10. KOH of tinea versicolor:
Molluscum contagiosum
Sandy like material in crater, children, self inoculate Poxvirus makes these (DNA virus)
13. Molluscum contagiosum:
Pityriasis Rosea
Example: rash on butt – non pruritic rash, NON INFECTIOUS; oblong looking with red on outside and pale in middle. You think this is T corporis, but its oblong (and not circular). Do a KOH prep, find nothing; then put topical steroids and doesn’t go away; 3 days later comes back with rash in the line of langer in Christmas tree like distribution; not an infectious dz, like a herald rash; not a fungus
22. Oval herald patch in pityriasis rosea: the lesion looks like tinea corporis but is not infectious (Drm022)
23. "Christmas tree" distribution of the rash of pityriasis rosea
Dysplastic Nevus syndrome
Example: precursor lesion for malignant melanoma; if you have over 100 nevi all over body, you have dysplastic nevus syndrome
Very common
Must go to dermatologist once a year bc need to look at dysplastic nevi. Could be a precursor lesion for malignant melanoma.
4 diff types of malignant melanoma What is first step in management? Excision
Example: superficial spreading malignant melanoma (MC)
Example: on face of older pt – Lentigo maligna melanoma; irregular border, corn colored, LEAST likely to met of all malignant melanomas.
Example: black pop’n do not get malignant melanomas bc the black pigment in the skin prevents UV light damage and propensity for cancer.
however, there is one type of cancer they malignant melanoma they CAN get: black pt with dyspnea, on xray find multiple mets all over body.
Bx is done and pt has malignant melanoma, which part of the body would you examine to find the primary dz? Under the nails, palms or sole of the feet
– this is Acrolentiginous malignant melanoma (‘acro’ means edge of/tip of) – this is the MOST AGGRESSIVE of all the melanomas.
– This has nothing to do with radiation. – Pagets dz looks similar
Example: Nodular malignant melanoma – also very aggressive.
The most important thing affecting prognosis is depth of invasion (key to prognosis – magic # is .76 mm). If its less than .76, its not gonna met.
Toxins
2 poisonous spiders – Black widow
Has a neurotoxin – causes spasm of the muscles in the upper thighs and abdomen so strong its almost like tetanus; pain muscle contractions, esp in the abdomen. There is an antivenom, painful bite
Example: person went down into their cellar, lifted boxes, felt sharp prick on finger, and developed contractures over a period of hrs – due to black widow bite.
Brown recluse spider (aka violin spider) Painless bite, has a necrotoxin, leading to ulcer
So, neurotoxin for black widow, necrotoxin for brown reclous
Where is receptors to androgens? Sebaceous glands (this is why men get more zits than woman – testosterone will release lipid rich material which gets into the hair follicle. Then, if you have proprionum acnei (anaerobe) it has lipases that breakdown fat from the sebaceous gland and produces FA’s that irritate the follicle and end up with acne. So, men more likely to get it bc they have acne
It all occurs in the erector pili muscle of the skin.
Drug used to prevent hirsutism? Spironolactone (same drug used to block
aldosterone); this drug is good bc it blocks androgen receptors and therefore prevents hirsutism. Can also lead to gynecomastia.
CNS
Spinal fluid – derives from choroid plexus in the ventricles. In the lateral, 3rd and 4th ventricles. Its an ultrafiltrate of plasma.
What is the difference in serum and spinal fluid? Way more protein in spinal fluid bc it’s an ultrafiltrate.
Cell? Hardly any cells in spinal fluid (none).
Glucose? Lower in spinal fluid – about 60% of what it is in serum (if the spinal fluid glucose level were low, then something is in there utilizing it for energy such as bacteria or fungus or cancer cells).
Is there anything MORE in spinal fluid than serum? Chloride (way higher in spinal fluid than serum) - around 120.
These are imp bc there are injuries to the head.
Example: baseball that hits the eye in an orbital blowout fracture – can potentially break cribriform plate, leading to dripping fluid out, which could be snot, serum, or spinal fluid. So, its imp to know diff’s btwn the two.
Example: wacked in the head – fluid out of ear (otorrhea), hemorrhage leads to battle sign.
This is a fracture of the basilar plate and there is spinal fluid there.
Most of the fluid comes out the aqueduct of sylvius – which is the MCC of
hydrocephalus in children bc it gets blocked off until you get a build up of spinal fluid in the 3rd vent and lateral vent, which is a narrow area and leads to hydrocephalus.
Then, it comes to the fourth vent and needs to get out bc it needs to get into the subarachnoid space.
So, it goes through the foramen of Luschka and Magendie, so fluid goes out. Dura means strong – it’s tightly adherent to the periosteum.
So, when pt has epidural hematoma (blood clot betwn bone and dura).
The only pressure that can split the periosteum away from dura is arterial pressure. So, this is the one when the middle mengial artery ruptures, and can be done with arterial pressure (not venous).
It gets into the subarachnoid space (to protect us – a cushion against damage). Get rid of spinal fliud in arachonoid granulation.
It goes through the arachnoid granulations, (there are NO LYMPHATICS IN BRAIN) and the dural sinuses and conglomerate into the jugular vein, which is emptied into the right side of the heart.
So, when you do a valsalva and the neck veins distend, that pressure transmits all the way back to the dural sinuses, to the arachnoid granulations through the spinal fluid , and right down the the needle in the subarachnoid space at L4 and the pressure goes up.
This is called quakens step maneuver.
It is a great test for when you are doing a spinal tap to see if the entire subarachnoid space is patent.
If you don’t see that manometer go up, there is something blocking the spinal fluid more proximally.
Example: when you wt lift, you shouldn’t hold your breath bc the pressure are huge and and lead to a herniated disk.
Tentorium Cerebelli
70% of brain tumors in adults are supratentorial (involve cerebral cortex) 70% of brain tumors in kids are infratentorial (cerebellar, cystic astrocytoma, medulloblastoma)
Hydrocephalus
Communicating vs Noncommunicating
Communication of spinal fluid in ventricles with subarchnoid space. Noncommunicating
MC
Something is preventing spinal fluid in the ventricles from getting into the subarachnoid space
MCC = stenosed Aqueduct of Sylvius
Or something going in the 4th vent, ependymoma in kids will block it off, or meningitis in
base of brain (TB), leads to scar tissue bc blocks foramen of magendie and luschka. Communicating
Still communicating, but still a build up of pressure.
One cause could be tumor of choroid plexus (papillary looking).
So, if you have a tumor there, you have a greater ultrafiltrate of plasma and would be making more plasma.
Also, would be making more spinal fluid.
There would still be a communication with here, but the pressure would build up bc making more than you commonly do.
More commonly, what if you have a subarachnoid bleed or meningitis? Then pt has scarred off arachnoid granulations and have no way of draining it out.
Arnold Chiari Malformation Example: pull down spinal cord.
This would bring the medulla into the cervical region and maybe a lil part of the cerebellum.
Leads to hydrocephalus and platybasia (flattening of the base of the skull) Dandy walker syndrome
Cerebellar vermis is not developed Herniation
Why would we herniate in the brain? Bc there is cerebral edema and no other place to go.
The famous ones are tonsillar herniation through the foramen magnum. (from the cerebellum) – cerebellar herniation – has been squeezed into the foramen magnum, and has constriction.
Can cause immediate death.
Uncal herniation – medial portion of the temporal lobe herniates through the tentorium cerebelli and pressing against midbrain, leads to hemorrhage (duret’s hemorrhage). Also an oculomotor nerve that is gonna be compressed.
So, this will lead to opthalomoplegia (LR6SO4, 3), so everything innervated by CN III is paralyzed.
With oculomotor nerve palsy, it is down and out.
(down and in is CN 4 palsy – if CN 6 is paralyzed, will look cross eyed). Look at pupil. Example: MRI of oribit, name muscles
Parasympathetic constrict the pupil (normally) , sympathetics dilate (normally) So, if you mess up the parasympathetics, which normally constrict, it will lead to mydriasis.
The first sign of uncal herniation is mydriasis of pupil on side of herniation (so it dilates on that side).
Also, posterior cerebral artery can get blocked with uncal herniation, leading to post lobe infarction.
Know brainstem and CN’s and how it related to herniation Papilledema
Any cause of increased incranial pressure Vit A tox
Lead poisoning – delta-aminolevulinic acid – leads to increased permeability