1. Digoxin Toxicity
– Most common symptoms are GI: nausea, anorexia, vomiting
– EKG: bidirectional ventricular tachycardia and accelerated junctional rhythm (AV node outpaces SA node due to stimulation and suppression respectively). You also may see scooping T-wave depressions (pretty characteristic of digoxin toxicity)
– Visual symptoms - "yellow halos" around objects
– May be 2/2 verapamil which decreases renal clearance of dig
– Anything that affects renal function/GFR will affect dig levels
– Target levels 0.8-2.2
– Treat with digitoxin Fab (Digibind is >$10,000 per vial). Mag and lidocaine may help. Check and replenish lytes.
2. Vaccinations in HIV
– Generally should not be given live vaccines, except MMR, varicella, zoster and yellow fever if the CD4 count is > 200 & the patient has never had an AIDS defining illness
– Should get TDaP q10, pneumococcus, hep A (MSM only), hep b, HPV
– Meningococcus: same indications as not HIV- college student, military, no spleen, travel to endemic areas
– HiB if not given in infancy
3. Endocrine: 
- Metabolic derangements in hypothyroidism: hyperlipidemia, hyponatremia (from increased water retention), increasing creatinine kinase, transaminitis
- Thyroid disease can affect deep tendon reflexes and muscle tone .
- Low T with low FSH and LH suggest central cause. Should check prolactin levels = if they are high then MRI
- Cushing's can cause shift neutrophilia
- Management of SIADH - fluid restriction and salt tablets -/+ loop diuretics. Hypertonic saline in resistant cases. Demeclocycline is an anti-ADH but It can be nephrotoxic and is rarely used
- Hyperparathyroidism can cause elevated calcium levels in the blood which leads to chondrocalcinosis and pseudogout
- Familial hypocalciuric hypercalcemia has mutated calcium sensing receptors in both kidney tubules and parathyroid gland leading to inappropriately high-normal PTH.
- Calcium to creatinine ratio greater than .02 suggests calcium losing process such as primary hyperparathyroidism; Ca-to-Cr ratio less than 0.01 suggests calcium retaining process such as FHH
- Low Ca AND low phos: think vitamin D deficiency (chronic pancreatitis, decreased absorption of fat soluble vitamins) or acute pancreatitis
- Low C and high phos: primary hypoparathyroidism or pseudohypoparthyroidism (body can't respond to PTH)
- Immobility can cause hypercalcemia: possibly due to increased osteoclastic bone resorption. Usually occurs about 1 month in, but people with renal insufficiency can see it in days. Treat with bisphosphonates.
4. Ectopic ACTH production
– Can occur in small cell and carcinoid
– If ACTH production is slow you will get a cushingoid symptomatology
– If ACTH production is high then You get a hyperaldosteronism picture along with hyperpigmentation. Cortisol has high affinity for mineralocorticoid receptors, however it is normally rapidly converted to inactive cortisone by 11 beta HSD in kidney tubule cells, However the acute and high ACTH production saturates the enzyme.
5. Vitamins: 
- Serotonin syndrome can lead to niacin deficiency; the increased synthesis of serotonin shunts tryptophan away from niacin synthesis. Diarrhea dermatitis dementia and death.
- Vitamin A overdose can cause pseudotumor cerebri. Headaches and blurry vision. Dry skin. Abdominal pain
- B12 deficiency - think pernicious anemia - think gastric cancer
- Give B6 and folate supplements to reduce levels of homocystine in homocystinemia. Homocystine is highly reactive and predisposes to venous clots and atherosclerosis. Homocysteine can be broken down into methionine (requires B12 and folate) or into cysteine (requires B6).
Vitamin K: onset of action 8 to 12 hours when given iatrogenically. Most people have a 30 day supply In the liver but those with underlying liver disease can become deficient in 7 to 10 days
6. Going back to the Pharm: 
- Aspirin hypersensitivity reaction: Shunting of arachidonate acid to leukotrienes by cox inhibitors in susceptible individuals leads to nasal polyps and bronchoconstriction. Treat with leukotriene inhibitors
- Aspirin can cause idiopathic thrombocytopenia
- Primodone is an anticonvulsant that breaks down into phenobarbital. This can precipitate acute intermittent Porphyria. It is used to treat essential tremor.
- Sildenafil should not be combined with nitrates, or any other vasodilators as it can worsen hypotension. If you're administering with alpha blockers like doxazosin, wait 4 hrs in between to prevent hypotension.
- Trihexiphenydil - Anticholinergic like benztropine. Used to treat Parkinson's and dystonia from anti-dopaminergics
- Drugs that can cause pseudotumor cerebri: vitamin a derivatives (all trans retinoic acid, accutane), tetracyclines, growth hormone
- Side effects of epo:  Worsening hypertension, headaches, flu like symptoms, rarely red cell aplasia
- Fluphenazine: high potency typical antipsychotic. Injectable, long lasting. Can inhibit shivering response and lead to significant hypothermia in cold environments.
7. Management of anemia
– Defuroxime to manage iron overload in patients with frequent transfusions (B thal major or sickle cell)
– Folate supplementation in patients with high red cell turnover ie hemolysis (PNH, HS, sickle cell) or B thal
– No treatment for b thal minor
– Prednisone for AIHA
– Indications for epo: CKD anemia, anemia of chronic disease, anemia after bone marrow transplant or chemo
8. More heme: 
- Lupus anticoagulant causes falsely elevated PTT by binding to phospholipids in the test. Mechanism of thrombosis unknown: possibly concentration of antibodies on cell surfaces causing activation of coagulation cascade
- Polycythemia vera causes gout in up to 40% of people. Characteristic pruritus after a hot bath due to increased histamine released from increased basophils. This increased histamine secretion can also lead to gastric ulcer. Splenomegaly.
- Isolated thrombocytopenia: test for hep C and HIV (can cause isolated cytopenias). Other causes: EBV, myelodysplastic (age>60), alcohol, B12 or folate deficiency.
9. Neuro 
- Diplopia after prolonged eye use, dysarthria after prolonged speaking, or jaw fatigue after prolonged chewing = Think myasthenia gravis. CPK will be normal which distinguishes it from primary muscle pathology. Reflexes will be normal which distinguishes it from ALS.  Approximately 15% of those with MG have a thymoma. MG tends to affect bulbar muscles first.
- Alcoholic cerebellar degeneration causes typical cerebellar signs such as dysmetria and dysdiadochokinesia as well as ataxia and truncal ataxia. You can also see muscle hypotonia leading to pendulum swing (striking of patellar tendon leads to slow pendulum like swinging of the leg - more than four swings is considered pathologic)
- Clasp knife rigidity and clonus are pyramidal signs
- Hemineglect: parietal lesion.
- Achilles tendon reflexes often fade With age
- Distinguishing dementia from typical aging. Dementia is:impairment of normal functioning, loss of insight about memory loss and declining functioning (anosognosia), not only expressive but some receptive aphasia, getting lost in familiar environments, losing the ability to remember recent important memories
- After sub-arachnoid or intraparenchymal bleed, you can see cerebral salt-wasting 2/2 SIADH and secretion of BNP (which wastes salt)
10. ID in HIV 
- Causes of dysphagia in HIV patients: Candida most common overall. Causes mild to moderate esophagitis and is usually associated with thrush. Severe pain + no thrush think CMV or HSV
- Candida: empirically treat with 3-5 days fluconazole. If it's resistant you can go to voriconazole, caspofungin or amphotericin
- If there is no thrush or does not respond to treatment you should scope to look for CMV (linear ulcers) or HSV
- Treat apthous ulcers with topical steroids, and if that fails, systemic steroids
- Treat CMV with ganciclovir: CMV does not include the viral thymidine kinase needed for acyclovir to be effective
- Pentamidine is the treatment for PCP pneumonia in AIDS patients who cannot tolerate bactrim

1. Upper lobe lesions in the lungs
– Aspiration while supine: rapid onset, very sick patients
– TB: chronic course
– Primary cancer: usually one lesion
– Mets: uncommon, these tend to occur more in the lower lobes where there is better more blood
– Histo, blasto.
– Aspergillus fungal ball.
2. Rheum to grow: 
– Ankylosing spondylitis: primarily involves the apophyseal (= facet) joints.
– Arthritis pain that occurs in a young person, symptoms occur at night, and improve with exercise => think inflammatory arthritis. (most injury or degenerative arthritis is worse with exercise, improve with rest and doesn't have nighttime symptoms)
– Manage lupus with limited skin and joint involvement with hydroxychloroquine. Do eye exams q6 months as this drug may cause retinopathy or corneal damage.
– Dermatomyositis is associated with an increased risk of internal malignancy. Up to 10% of people with adult onset DM will develop malignancy. DM is six times more common in women than men. The most common cancers are ovarian, breast, lung, uro-gyn malignancies
– Treat inflammatory polymyopathies with high dose steroids
– Treat reactive arthritis with NSAIDs

- Stills disease: maculopapular rash that occurs on the trunk and extremities that coincides with fever and joint pain

3. Complications of rheumatologic disease 
– Aortic aneurysm: behcets, Takayasu, giant cell, the seronegative spondyloarthropathies notably AS, RA
– Renal failure: Wegener's, lupus, Goodpasture's, HSP, PAN, Scleroderma
– Alveolar hemorrhage: churg Strauss, Goodpasture's, wegners, behcet
– Pulmonary fibrosis: dermatomyositis, scleroderma
– Carpal tunnel: sarcoid, amyloidosis, RA (can also happen in hypothyrodism)
– Mononeuritis multiplex: Churg Straus, PAN, Wegener's, lupus, amyloid,sarcoid,  cryoglobulinemia, RA
4. Amyloidosis
– Primary AL, secondary AA - Chronic Inflammatory state like RA, IBD, chronic infections (Bronchiectasis, osteomyelitis, TB), Cancer, vasculitis
Manifestations:
– Cardiac - hypertrophy without change in chamber diameter
– Renal: nephrotic syndrome
– Neuropathy : Autonomic (orthostatic hypotension), peripheral neuropathy (carpal tunnel syndrome)
– Hepatomegaly
– Other organ enlargement like macroglossia
– Waxy skin
– Easy bruising/bleeding diathesis
– Colchicine is used in the prophylaxis and treatment of AA amyloidosis
5. Stuff that crystallizes in your kidney tubules 
- Acyclovir
- Protease inhibitors (indinavir)
- Ethylene glycol (ca-oxylate crystals - envelope shaped crystals)
- Sulfa drugs
- Methotrexate
- Stuff that gives you AIN - B lactams, PPIs, usually takes 7-10 days
6. More renal stuff 
– Nephrotic GN: Membranous, diabetes, IgA, Amyloidosis, minimal change, FSGS
– Mild Nephritic GN: thin basement membrane syndrome, IgA, lupus
– Moderate/severe Nephritic GN: Post strep/infectious, membranoproliferative, lupus, vasculitis,  RPGN
– If a patient with pyelo does not respond after 48-72 hours of appropriate antibiotics, urologic imaging (CT or ultrasound) is indicated to look for complicating pathology like an obstruction or abscess
– Hypertensive nephropathy: characterized by increased pressures, leading to nephrosclerosis, that is, fibrosis of the renal arterioles, progressing to sclerosis of the glomerular capillaries
– Diabetic nephropathy: characterized by increased filtering, leading to increased extracellular matrix, thickening of the glomerular basement membrane, and mesangial proliferation
– Analgesic abuse nephropathy: characterized by focal glomerulosclerosis. Its a tubulointerstitial disease. Additionally analgesia mediated vasospasm of the vasa recta => papillary necrosis resulting in painless hematuria. On UA the red cells appear normal, in contrast with glomerular sources of bleeding where the red cells appear dysmorphic. The bleed can be significant to where the blood clots will cause renal colic.

- Acetylcysteine has been shown to decrease IV contrast nephropathy, perhaps because of its antioxidant and vasodilatory properties 

- Goodpasture's disease: you make anti-glomerular basement membrane antibodies. Treat with immediate plasmapheresis to prevent renal injury. 

- Treat Wegener's with cyclophosphamide and steroids

- Prednisone can cause fluid retention in people with renal failure 

7. Everybody loves ID 
- Treat bartonella henselae with five days of Azithro
- Influenza can cause proteinuria and leukopenia - there's data that h5n1 virus destroys lung epithelial cells and leukocytes in replication.
- Viruses that cause myocarditis: Coxsackie B, adeno, entero, parvo, HHV-6
- Colitis and pneumonia one month post bone marrow transplant: think CMV. Diarrhea and other GI symptoms caused by ulcers.
- Hepatitis B initially goes through an immune tolerant phase where the virus replicates; AST and ALT are low, HBV DNA and E Antigen are high. Then there is an immune clearance phase where the body starts to attack infected hepatocytes. ALT rises, biopsy shows inflammation in the liver, and markers of Hep B Infection ( E antigen and viral load) fall during this. Follow ALT and HBeAg q3-6 months to ensure total clearance.
Palm and sole rash:
- syphillis secondary and congenital (copper)
- RMSF (outside in) and typhus
- Kawasaki, TSST, measles (peeling)
- coxsackie A / hand foot mouth
Others: contact dermatitis, lupus, erythema multiforme
8. Measles (rubeola) vs rubella  
- both have same prodrome - cough, conjunctivitis, coryza, lymphadenopathy
- measles has higher fever > 40
- rash moves from head down, fast in rubella, slow in measles
- rubella associated with arthritis in women older than adolescent age (not men or children)
9. CML versus leukemoid reaction
– Both = leukocytosis with marked left shift
– Leukemoid reaction is a response to severe infection / Inflammation
– Leukocyte alkaline phosphatase is the critical distinguishing factor. It will be elevated in leukomoid but decreased in CML
– CML blast crisis is where CML behaves like AML: > 20% blasts on peripheral smear
10. GI stuff 
– Melanosis coli: Brown Stained colon with white patches representing Lymphoid tissue, 2/2 Dulcolax/Bisacodyl (ab)use
– GI angiodysplasias are often diagnosed in the setting of acquired coagulopathy, such as acquired von Willebrand disease (aortic stenosis => shearing of large VWF multimers) or uremic platelet dysfunction 2/2 ESRD
– Hemolytic anemia + acute onset transaminitis and ascites: think PNH. PNH predisposes to venous clots, particularly in hepatic veins.

- Chronic portal vein thrombus can present as varices

1. Glucagonoma

- Derm: erythematous plaques that can coalesce and blister around perineal area, extremities, face

- Neuro: ataxia, dementia, proximal muscle weakness

- Can cause increased DVT

- Serum glucagon > 500.
- Other conditions that cause elevated glucagon: cushing's, pancreatitis, sepsis and hypoglycemia, although in these cases serum glucagon is generally < 500 

2. Theophylline toxicity 

– CNS stimulation – Headaches, insomnia, seizures

– G.I. disturbances: nausea and vomiting

– Arrhythmias: Atrial tachycardias, SVT, v-tach

– Narrow therapeutic window, levels can be increased by CYP inhibitors (macrolides, Verapamil, cimetidine, cipro), by acute illness and by cirrhosis.

3. DDx SVC Syndrome

– Malignancy: lung cancer, non-Hodgkin's lymphoma

– Fibrosing mediastinitis: 2/2 Histo, TB 

– Giant clot from an indwelling line 

4. Hep C cryoglobulinemia: 

– Think of it like lupus with elevated transaminases: vasculitis of skin, kidneys, nerves, joints.
– Renal: proteinurea and hematuria 

– Skin: Palpable Purpura. 

– Joints: Arthralgias
– Systemic inflammatory symptoms: malaise, fatigue

– Nerves: peripheral neuropathy

– Hepatosplenomegaly

– Labs: Decreased complement (low C3, C4), elevated RF. 

5. DDx Pulsus paradoxus

– cardiac tamponade

– Severe asthma or COPD 2/2 significantly increased intrathoracic pressure on inspiration - sucks blood out of the heart into the pulmonary venous system, reducing preload 

6. Dermatology 

– Tinea versicolor: flat white pink or brown macules that do not tan, scale on scraping. Treat with ketoconazole or selenium sulfide. 

– Seborrheic keratosis: brownish stuck on lesions
– Seborrehic dermatitis: rash that affects anywhere with sebaceous glands (face, intertriginous, parasternal, scalp). Greasy yellow scale over erythematous base. Often associated with underlying Parkinson's or HIV.

– Tinea corporis: erythematous rings with scaly edges 

– Pityriasis rosacea: flat fawn colored macules up to 2 cm, christmas tree, herald patch

– Sudden onset seborrheic dermatitis or severe psoriasis - think HIV or GI malignancy 

– Photo allergic contact dermatitis can occur with certain kinds of sunscreen. Prior exposure is needed

7. Optho 

- Tarsal conjunctiva = conjunctivae lining the inside of the eyelid. Granular appearance suggests viral conjunctivitis (among other things). Treat viral conjunctivitis with cool moist compresses

- Macular degeneration causes central vision loss - can be atrophic with sores or proliferative with increased blood vessels.

- Open angle glaucoma causes loss of peripheral vision and is more common among diabetics. On exam you will see increased cupping. 

- Acute closed angle glaucoma: hard eye, dilated/fixed pupil, blurred vision, halo, pain, conjunctivitis, headache, nausea. Treat with pilocarpine to open canals of schlemm and timolol to reduce synthesis of aqueous humor. 

- Anterior uveitis: inflammation of uvea, especially iris. May have conjunctival inflammation next to cornea is usually spared. 

- Conjunctivitis vs keratitis: keratitis implies involvement of cornea. 

- Fungal keratitis is often found in agricultural workers and immunocompromised patients; you'll see multiple stromal abscesses

- Bacterial keratitis is common in contact lens wearers (particularly gram negatives like pseudomonas and serratia). The cornea will appear hazy with a central Ulcer and surrounding stromal abscess-  you may see hypopyon. 

- Herpes simplex keratitis: recurrent infections triggered by sun exposure (outdoor work) fever or immunodeficiency and are characterized by dendritic ulcers & corneal ulcers

- Episceritis: mild pain and discharge. RA, IBD. Does not affect vision or cornea. 

- Standard diabetic retinopathy includes micro hemorrhages and cottonwood spots

- Central Retinal vein thrombosis causes sudden loss of vision often in the morning; you will see dilated and torturous veins on exam, and disc swelling

8. Indications for aortic valve repair in aortic stenosis

– Any symptoms: Syncope, dizziness or lightheadedness, dyspnea

– Significant stenosis in a patient getting a CABG or other valve surgery

– Significant AS + plus poor LV function, poor exercise tolerance, or significant LV hypertrophy

9. Liquid cancer treatment

– Hairy cell: cladribine (purine analog) 

– CLL: prednisone plus chlorambucil

– Non-Hodgkin's: CHOP
- Hodgkins: ABVD (adriamycin, bleomycin, vincristine, dacarbazine)
- APML: All-trans retinoic acid
- AML: induction (cytarabine + anthracycline like daunorubicin) + consolidation (more chemo drugs or stem cell transplant depending on cancer genetics) 

10. NAFLD

– Due to insulin resistance => increased peripheral lipolysis, which is taken up by the liver 

1. Medical management after MI: 
- ACE inhibitors prevent ventricular remodeling (i.e. aneurysm information after MI)
- Carvedilol may actually be able to to reverse remodeling 

2. Oral leukoplakia is a precancerous lesion. It will resolve with cessation of tobacco or alcohol. Transformation into a more nodular or ulcerated or indurated appearance suggests transformation into squamous cell carcinoma 

3. Vaccinations 

- HiB: Asplenia 

- Pneumococcus: everyone >65. If given to an HIV-positive person with a CD4 < 200 you should repeat when CD4 is higher.  Repeat at five years. 

- Indication for early pneumococcus: No spleen, chronic heart lung liver kidney disease, diabetes, alcoholics, smokers, cochlear implant, CSF leak, immunocompromised 

- Meningococcus: college students, military recruits, no spleen, travel to endemic areas. Can repeat At five years if still at risk. Indications for meningiococcus vaccine in HIV+ is same as in HIV-

- Hepatitis A – travel to endemic areas, MSM, IV drug use, concomitant hep B or hep C or liver disease that would amplify the consequences of hep a infection 

- Tetanus – TD q10, replace one of these with TDaP before 65 

4. Fibromuscular dysplasia in unilateral renal artery should be treated with stenting if the hypertension was recent onset or the hypertension cannot be managed with meds due to intolerance or ineffectiveness. The goal of stenting is to treat the hypertension. 

5. Dementias: 
- Alzheimer's disease: memory is first, then visual spatial, then later on possibly executive function, urinary incontinence, gait abnormalities

- NPH: marked gait abnormalities are the first presenting symptom. Later on, you get dementia and incontinence

- Lewy body dementia: visual spatial is affected first, and then memory later on. + Parkinsonian features. 

- Vascular dementia: In the early stages has significantly more executive function impairment than memory impairment 

6. PTU or methimazole
- If someone develops a fever and sore throat while taking these drugs, discontinue and check CBC. White count < 1000 = likely agranulocytosis (immune mediated destruction of granulocytes). If WBC > 1500, it's unlikely to be agranulocytosis.
- Treat PTU or methimazole induced agranulocytosis with IV broad-spectrum antibiotics - cover for Pseudomonas 

7. Acute Pancreatitis: 

- Viruses that cause: Mumps, HIV, coxsackie, CMV, HSV, Hep B

- Can present with ileus, lung pathology (including pleural effusions, atelectasis, ARDS due to release of enzymes and cytokines and pancreas -> systemic inflammation). 

- Clinical presentation ranges from very mild epigastric tenderness on palpation or severe abdominal pain with rebound/guarding. Occasionally the pain is made better with sitting up or leaning forward.

- Vs: Intra-abdominal abscess has a more indolent Course

8. AIDS CNS pathology 

- EBV DNA in the CSF is very specific for primary CNS lymphoma

- PML presents with unilateral weakness, changes in vision and hearing, and ataxia

- CNS toxoplasmosis infection is unlikely in someone taking bactrim 

9. Cystinuria 

- Decreased renal reabsorption of dibasic amino acids such as cysteine, arginine, ornithine, lysine

- Hexagonal crystals in the urine.

- Urine cyanide nitroprusside test + (test for urine Cysteine)

10. Drugs That cause hyperkalemia

- Bactrim inhibits ENaC transporter. It also causes an elevation in creatinine that is not associated with renal injury. And causes pseduo-type 4 RTA. 

- Beta blockers (notably B2 receptor, hence why you use albuterol to treat hyperkalemia) 

- Digoxin-  from blocking Na/K ATPase

- Heparin inhibits aldosterone synthesis

- Cyclosporine inhibits aldosterone activity

- NSAIDs - harm kidneys, reduce aldosterone

- ACE, ARB - Reduce aldosterone

- K Sparing diuretics 

1. Transfusion reactions 

- seconds to minutes -anaphylaxis. Anti IgA. Use washed RBC next time 

- minutes in someone on ACEI - transfusion hypotension from bradykinin in the blood, which is usually broken down by ace 

- within the first hour - hemolysis from ABO incompatibility. F/c, Flank pain, hemoglobinuria => renal failure, DIC

- minutes to hours - bacterial sepsis from contamination (pseudomonas can grow in the cold) - sepsis, shock, DIC

- within the first six hours it's either TRALI (donor anti-leukocyte reaction => pulmonary edema and interstitial infiltrates on CXR) or febrile Non-hemolytic Transfusion reaction (from stored cytokines in the blood). Prevent both with leukoreduced pRBC. 

- 24 hours to two weeks - delayed hemolysis due to minor antigens

- Occurs after two weeks - transfusion associated GVHD. Donor leukocytes engraft and replicate, and then attack the skin causing rashes, the liver causing hepatitis, the G.I. tract causing mucositis and diarrhea, and the bone marrow causing pancytopenia. Death rate is nearly 100% without a bone marrow transplant. Prevent with irradiated RBC. 

2. Preparations for pRBC

- Leukoreduction: reduce white cell component of packed RBC. Prevents non-hemolytic transfusion febrile reactions because it stops the accumulation of cytokines from remnant white cells. It also stops the transmission of CMV so it's good for patients who are CMV negative who you really don't want to get CMV, such as AIDS patients, people awaiting transplant or status post transplant. Leukoreduction is also good for preventing HLA sensitization and thus is good for people who are going to need chronic transfusions. 

- Washing the cells will remove any plasma antibodies. This is especially good for people are IgA deficient and will have anaphylactic reaction to IgA in transfused blood. 

- Irradiating blood causes cross-linking of DNA which prevents replication of transfused leukocytes.  This is to prevent TA-GVHD. Someone with a a normal number of functional T-cells will be able to destroy the transfused white cells. But people with congenital T cell immune deficiencies (such as Wiskott-Aldrich, SCID), bone marrow transplant recipients, premature infants and fetuses, can't. Also people receiving transfusions from close relatives - because the HLA is similar enough that the recipient T cells will not recognize the donor cells as foreign.  

3. Microangiopathic Hemolytic Anemia (MAHA): In all causes, the mechanism is the formation of a fibrin mesh due to increased activation of coagulation. The red blood cells are physically cut by these protein networks => schistocytes.
- Valves: Rapid acceleration, fragmentation, and collision jets were associated with high shear stress and hemolysis whereas slow deceleration and free jets were not.
- Malignant HTN: The characteristic vascular lesion is fibrinoid necrosis of arterioles and small arteries, which causes the clinical manifestations of end-organ damage. Red blood cells are damaged as they flow through vessels obstructed by fibrin deposition, resulting in MAHA.
- TTP: <5% ADAMTS-13 activity + presence of ADAMTS13 inhibitor + clinical symptoms of an acute thrombocytopenia and evidence of MAHA, appropriately defines a diagnosis of TTP. Because the sensitivity of ADAMTS-13 deficiency it is not well established, a deficiency of the protein alone does not constitute a diagnosis of TTP.
- TTP + pregnancy: The association of pregnancy with TTP may account for some of the hypercoagulable risk in women near term and postpartum. In a large study of TTP cases, 10% of all cases were diagnosed during pregnancy or postpartum, with the majority of episodes occurring near delivery.
- HUS: kids < 4-5 years, prodrome of bloody diarrhea caused by shiga-toxin producing EHEC (0157:H7). 5-10% with  0157:H7 present with acute HUS. Thrombocytopenia, MAHA, and renal failue. The toxin binds glycolipid surface receptor on endothelial cells under the influence of inflammatory cytokines => platelet clumping.
- HELLP: preeclampsia + MAHA + thrombocytopenia. Usually resolves within days following delivery. The risk of TTP in subsequent pregnancies is hard to determine.
4. TTP & Drugs: quinine (common), mitomycin, penicillin, oral contraceptives, and anti-platelet agents (ticlopidine and clopidogrel)
- Mechanism: either antibody vs drug => immune destruction or direct side effect.
- Make quinine-dependent platelet antibodies => make antibodies to multiple target tissues, which result in the systemic involvement seen in TTP.
- Mitomycin: dose-related effect, causes MAHA and thrombocytopenia. Onset may be sudden due to the initial toxicity or may appear gradually due to the cumulative toxicity of the drug. Most patients in this category responded well to plasma exchange.
- Ticlopidine and clopidogrel: deficiency of ADAMTS-13 and an inhibitor of ADAMTS-13 activity has been noted. Most respond to plasma exchange.
5. Lesser known hemoglobinopathies: 
- Hb S-B-thal: When you make all Hb S and no Hb B-thal (called sickle cell-beta zero thalassemia), it's almost identical to sickle cell disease. When you make some B-thal (called sickle cell-beta plus thalassemia), the condition is less severe.
- HB lepore: similar to beta-thalassemia (electrophoresis and smear); decreased hemoglobin synthesis. Homozygous Hb Lepore is rare. Patients of Balkan descent have the most severe presentation of - severe anemia during the first five years of life + significant splenomegaly, hepatomegaly, and skeletal abnormalities similar to homozygous beta-thalassemia. The amount of Hb Lepore in the patients blood ranged from 8 to 30%, the remainder being fetal hemoglobin (Hb F). Homozygous Hb Lepore is similar to beta-thalassemia major, however the clinical course is variable. Patients with this condition typically present with severe anemia during the first two years of life. The heterozygote form is mildly anemic (Hb 11-13 g/dl) but presents with a significant hypochromia and microcytosis.
6. Electrophoresis vs HPLC : 
- Electrophoresis allows the simultaneous study of about 90 samples on a single plate, using a central cathode and two anodes. At a glance, any band with abnormal mobility is detected as well as the absence of the normal Hb A band. This method is considered as a first line test and requires a confirmation by a second one, usually CE-HPLC.
- HPLC allows quantitative detection of Hb S and of the most common Hb variants
7. Fluid where there shouldn't be fluid: 

- Lymphocytic pleural effusion - think granulomatous disease such as TB or sarcoid, lymphomas or RA
- Hepatic hydrothorax: typically R sided, manage first with diuretics and salt restricted diet, if that fails consider TIPS if the synthetic function is holding, and there are no contraindications. If TIPS is contraindicated consider pleurodesis.
- Pathophysiology of Baker's cyst: Inflamed synovium produces excess synovial fluid which overflows into the popliteal burs => cyst. If the cyst bursts it can release it's fluid contents into the calf causing an appearance like a DVT; sometimes with crescent-shaped bruise over malleolus. These cysts are associated with RA, OA, and cartilage tears 

8. Transplant & Rheum drugs: 

- Methotrexate: Inhibits Folic acid usage and thus will affect rapidly dividing cells. It will cause G.I. disturbances like nausea/mucositis, alopecia, toxicities of the liver, macrocytic anemia and sometimes pancytopenia, interstitial lung disease, rash

- Hydroxychloroquine can cause visual disturbances, trigger G6PD, and cause G.I. disturbances

- Cyclosporine : Calcinurin inhibitor = will take down T cells - increases viral infections and lymphoma and can cause kidney damage. Also causes hyperplasia of gingiva + hirsuitism, hyperkalemia, hypertension (2/2 kidney effects), GI effects, increases risk of squamous cell carcinoma. 

- Azathioprine: toxic to the pancreas, liver, and bone marrow
- Prograf/Tacrolimus: hits your kidneys hard, narrow therapeutic window. Doesn't cause gingival hyperplasia or hirsuitism, like cyclosporine. Can also hit liver, heart. Also causes hyperkalemia and hypertension. 

9. Trousseau syndrome: migratory thrombophlebitis, seen in pancreatic, lung, prostate, colon, stomach cancer and acute leukemias. The tumors release mucins that react with platelets to form microthrombi. 

10. Infectious endocarditis

- Vascular manifestations: systemic thrombi to brain, spleen, or kidney, septic emboli to lungs, spleen. conjunctival hemorrhages, mycotic aneurysms, Janeway lesions (erythematous macules on palms and soles)

- Immune manifestations: arthritis, positive RF, glomerulonephritis (dark and cloudy urine 2/2 hematuria and proteinurea, Osler's notes (painful violaceous lesions on the fingers and toes), Roth spots (retinal hemorrhages)

- Specialized bacteria and their sources: Eikenella from oral cavity, strep bovis from occult colon cancer, enterococcus from complicated UTI, staph aureus from contaminated needles

1. Spontaneous bacterial peritonitis. 

- People with cirrhosis are often hypothermic so any temp > 100/37.8 warrants investigation 

- Ascites fluid with more than 250 Polys and a + culture are diagnostic 

- SAAG greater than 1.1 suggests portal hypertension as the source of the Ascites fluids and makes SBP more likely. 

- Treat empirically with third-generation Cephalosporin to cover enteric Gram negatives

- Other ascites facts: in pancreatic ascites, Amylase in the fluid is usually over 1000

- Secondary bacterial peritonitis occurs when there's a rupture of viscous organ into the ascites fluid. because the ascites separates the parietal and visceral peritoneum, the patient will not develop a rigid abdomen even with a raging infection. 

2. The most common cause of bloody diarrhea in the absence of a fever is EHEC.

- Test with stool Shiga toxin. 

- Treat supportively. 

- Do not give antibiotics as it increases the risk of HUS

3. Contraction alkalosis is mediated by Aldosterone. When intravascular volume drops, aldosterone secretion is increased, leading to renal excretion of protons and potassium

4. Rinne test 

- Put the tuning fork on the mastoid and then when the patient can't hear anymore you move it to the air in front of the ear. Air conduction should be twice as long as bone conduction. If this is not the case, thats considered abnormal and suggestive of conductive hearing loss

- Causes of conductive hearing loss: cerumen impaction, chronic otitis media or effusion, otosclerosis, bony tumors within the ear

- Otosclerosis causes conductive hearing loss in adults particularly in their 20s and 30s. It's thought to be potentially autoimmune. Stapes footplate becomes fixed to the oval window. There may be low frequency hearing loss. Treat with hearing aid or stapedectomy. 

5. The hepatojugular reflex is positive when the right ventricle is unable to handle the increased preload that comes from increased intra-abdominal pressure. 

- Causes include right heart failure, constrictive pericarditis (Such as TB), restrictive cardiomyopathy

6. General surgery smorgasbord: 

- No colonoscopy, sigmoidoscopy, or barium enema during acute inflammatory bowel process as the risk of perforation is high. 

- Diverticulitis that does not improve on antibiotics:: suspect intra-abdominal process/publication 

- Causes of toxic megacolon: IBD (UC that erodes through smooth muscle), c.diff, diverticulitis. Mange with bowel rest, pain control, antibiotics. Go to surgery if it doesn't resolve. 

7. Guillain-barre 

- Goes from legs up to arms and cranial nerves. 

- Progresses in hours to days. 

- Affects motor primarily, but can have distal paraesthesias. Can involve autonomic system and respiratory muscles, which can be life threatening. 20-30% of people will end up needing a vent.

- Track development of respiratory weakness and failure by serial measurements of vital capacity: <15mg/kg indicates significantly increased risk of respiratory failure. Other things like chest wall movements, or anything measured on spiro or peak flows or ABG or CXR are not as predictive as VC. 

- Treat with IVIg and plasmapharesis - steroids not indicated. 

8. Hepatic adenoma
- Common in young women with a long history of OCP use. Can also be seen with anabolic steroid use, pregnancy, diabetes glycogen storage diseases. Thought to be hormonal potentially but with unknown pathogenesis

- Path shows enlarged hepatocytes with cytoplasmic inclusions of lipids and glycogen. Nuclei are small and regular but hepatic architecture is distorted (no bile ducts etc)

- Can be found incidentally with imaging or labs (incidentally found LFTs). Elevated alk phos and GGT often indicate multiple adenomas or intratumoral bleed.
- Can present as collapse from rupture and intraabdominal bleed. Risk of bleed in symptomatic adenoma (ie abdominal pain) is 40%. 

- Do not biopsy as the risk of bleed is high.

- Manage symptomatic adenoma with resection. With asymptomatic, treatment is controversial, some resect b/c there is a risk of rupture or malignant transformation (8-13% of adenomas transform), others treat conservatively by d/cing OCPs, serial imaging and following AFPs. Many will spontaneously regress with this.  

9. Focal nodular hyperplasia is a benign tumor in the liver that arises from atypical blood vessels That cause hyperperfusion and local fibrosis. Biopsy shows Kupffer cells and sinusoids 

10. EBV mononucleosis typically will cause cervical lymphadenopathy and pharyngitis. While CMV mono generally does not.
Speaking of pharyngitis, EBV and group A strep are the most common causes; EBV tends to cause posterior LAD and splenomegaly, while GAS tends to cause anterior LAD and doesn't mess with your spleen. 

1. Empiric management of endocarditis: 

- Native valve: pen + gent. 

- Native valve, IVDU: nafcillin + gent to cover MSSA. vanc + gent if suspicion for MRSA

- Mechanical valve: cover MRSA, add rifampin for biofilm penetration 

- Replace vanc with linezolid if there is renal failure (issues with vanc levels) 

- Viridians strep endocarditis - IV penicillin continuous or q4-6 or once daily ceftriaxone for 4 weeks 

2. Don't treat HIT with Coumadin-- the rapid drop in protein c can aggravate the procoagulant state. Manage with argatroban or bivalrudin until platelets are > 150K, then you can start warfarin 

3. Some words on some drugs: 

- Bactrim covers s pneumo but not other strep species 

- Sodium bicarb blocks the effect of TCA on fast Na channels in cardiac tissue, hence the protective effect in overdose. 

- NSAIDs potentiate ADH and can lead to SIADH.

- Statins decrease  coenzyme q10 synthesis which is important for muscle energy - thought to be a possible etiology of the myositis. 

- Aspirin can trigger bronchoconstriction

- Alcohol sensitizies you to hypomagnesemia, increasing risk of torsades. 

- Drugs that prolong the QT: quinolones, macrolides, TCAs, class III antiarrhythmics 

4. Hemochromatosis 

- bronze DM

- hepatomegaly or cirrhosis (this disease is often diagnosed initially as incidentally raised LFTs on routine labs) 

- small testicle/decreased libido

- cardiac disease (dilated or restrictive myocarditis, conduction problems)

- Increased vulnerability to infections with listeria and vibrio vulnificus 

5. Splenic abscess

- Occurs in the setting of infective endocarditis (10-20% incidence?), immunosuppression (HIV), trauma, hemoglobin disease like sickle cell, IVDU. 

- Staph, strep, salmonella

- With antibiotics alone, there is a  50% mortality. Need splenectomy or percutaneous drain if they are too sick to go through surgery. 

6. Retropharyngeal abscess 

- Symptoms: trismus (pain w opening mouth), pain on neck extension, fever 

- Often history of local trauma (fishbone in throat) 

- Can dissect down into anterior or posterior upper mediastinum or all the way down the posterior mediastinum and cause necrotizing mediastinitis (requires urgent surgical debridement) 

- Vs: Meningitis, which has pain with neck flexion 

7. Back pain red flags

- Pain at night, not relieved by rest, not worsened with movement. 

- Bone that is tender to palpation, symptoms lasting > 1 month, age>50, 

- Get X-ray to r/o lytic lesion vs fracture, MRI if not diagnostic 

- Manage acute back pain with NSAIDs- acutely its better than PT. 

8. Acanthosis nigricans- DM or GI cancer

- More likely benign - young, obese person

- More likely malignant - older age. atypical locations such as mucous membranes, palms, soles

9. O2 supplementation in COPD: 

- In chronic COPD, people develop chronic hypercapnia and increased levels of deoxyhemoglobin, which has a higher CO2 affinity and increases carbon dioxide clearance. Adding oxygen blunts the amount of deoxyhemoglobin, decreasing clearance of CO2. 

- Acute hypercapnia: less myocardial contractility, lower seizure threshold, global loss of consciousness 

- Goal saturation for treatment of acute on chronic COPD with oxygen is 90-94% 

10. Polycythemia vera 

- causes gout in up to 40% of people 

- characteristic pruritus after a hot bath due to increased histamine released from increased basophils-  - - increased histamine secretion can also lead to gastric ulcer