VIRUSES: General Characteristics/Behavior Invasion Adhesion Penetration Uncoating Replication Assembly Lysogeny o Invasion RNA needs to get in to the

n to the cell Contact is the #1 way to spread infection Best prevention is HAND WASHING o Adhesion Viruses adhere themselves to the cell Viruses have receptors for certain cells Tropism o Penetration 99% will enter the cell via endocytosis Only HIV injects RNA into the cell o Uncoat Virus takes its capsule off removing envelope Drugs are helpful at this stage: Amantadine o Treatment for ONLY Influenza A o Inhibits uncoating of virus o Also, promotes the release of dopamine Used in Parkinsons o Anticholinergic effects Rimantidine o Indicated for prophylaxis

SE: Both will affect rapidly dividing cells Both effective if taken within 73 hours

Virus Type Location of Replication Polymerase

RNA Replicates in the cytoplasm Exception: Retrovirus Needs RNA dependent RNA polymerase Exception: Retrovirus requires RNA dependent DNA ploymerase

DNA Replicates in the nucleus Exception: Poxvirus (too large) Exception Poxvirus requires DNA dependent RNA polymerase Hep B requires DNA dependent DNA polymerase 90% DS Exceptions: Parvovirus Hepadenovirus (Hep B)

Strand Type

90% are SS Exceptions Orthomyxovirus (ds) Reovirus (segmented)

Assembly Negative or Positive Strand

Envelope

Assembled on cell membrane destroy cell membranes (recall AST/ALT) Negative Strand: Needs to be translated into + mRNA before getting translated Takes 1-3 weeks to get sick Positive Strand: Gets translated immediately making you sick immediately (hemorrhagic viruses) Assume an envelope Except: Coxsackie A (non-enveloped)

Assume Naked Exception: Herpes (enveloped) HIV is an retrovirus that goes to the nucleus Hep. B uses a reverse transcriptase Remember that if there is nuclear damage the cell dies think about rapidly dividing cells promotion of cancer

Misc

o Replication Insertion of RNA virus into your DNA genome and you do all the work Drugs are helpful at this stage 3TC, Pyrimidine Used in HIV 4TC, Pyrimidine Therapy DDI, Purine When CD4 < o SE: Painful neuropathy and pancreatitis 500 DDC, Pyrimidine o SE: Painful neuropathy and pancreatitis AZT o Bone marrow suppression (aplastic anemia) Acyclovir These are used to treat HSV I/II o 5x/day viral shedding Replace Pencyclovir Guanine symptomatic days o 3x/day NO CURE Demcyclovir Purine Outbreak within 2 weeks of o 3x/day Analogs delivery, need to perform C Valcyclovir section o 2x/day Gancyclovir o Cures CMV retinitis (AIDS patient with vision problems) o Foscarnet is the backup drug for CMV retinitis Fancyclovir o Used to treat Shingles (Herpes Zoster) o Herpes Zoster Resurfacing of chickenpox hide in the Dorsal Root Ganglia (1 dermatome) MC locations T4 level of the nipple Opthalmic Division of V1 MC reason for outbreak = STRESS Must do ELISA Test for HIV/Cancer patient if >40 y.o. with shingles Patient can complain of burning on the chest Ribavarin o RSV Treatment o Teratogenic and given aerosol No pregnant nurses are allowed to give this medication

o Assembly o Lysogeny Virus explodes out of the cell Destroys membrane RNA destroy cell membrane DNA destroy nuclear membrane Wrap themselves with cell membrane autoimmune disease 3

3 Stages: From Invasion Penetration Viremic and asymptomatic o There is not enough virus to cause illness o While in blood still able to perform tests (ELISA) Invasion Adhesion Eclispe o Virus is now hidden o Virus is in the blood but can no longer be detected o Need to run PCR, Southern Blot, or Northern Blot Penetration Uncoating Replication Viremic and symptomatic o Patient begins to deteriorate Assembly Lysogeny MCC Infections: Encephalitis = inflammation of the brain o Togavirus All end in equine The more e in the name the more lethal Mosquito carrier o Present with: Bad headache Ataxia o Self-limiting will go away by itself o Herpes virus the #2 cause of encephalitis Location Temporal Lobe = hemorrhagic Meningitis o Protein (inflammatory cell) is elevated in every meningitis Bacteria: glucose o If viral look for lymphocytes/monocytes neutrophils Will have normal sugar o Aseptic Meningitis NO BACTERIA INVOLVED MCC: Enterovirus (any virus that causes diarrhea GI) Fungus: Adult Adenovirus sugar Pediatrics Rotavirus lymphocytes Present with Headache & monocytes Common Cold sinusitis, otitis, bronchitis, pneumonia o Rhinovirus only common cold symptoms = sniffles o With any additional symptoms (cough, sore throat) = Adeno or Corona 4

o Adenovirus (fall/winter) #1 cause of conjunctivitis Associated with Cryoglobulinemia Described as necrotizing bronchiolotis in the lung o Coronavirus (summer/spring) o Influenza virus Cryoglobulinemia ( recall Strep. Salivarius) o Parainfluenzae o HSV-I Herpes Keratitis = inflamed cornea Steroids are contraindicated will cause loss of vision because the dendrites will rip throught the cornea Childhood Illnesses Mumps o Affects the parotids Acute parotidis o Inflammed parotid gland swelling in the front of the ear o Stensons duct appears red o Painful when asked to taste something sour (saliva cant be secreted to nullify acid) o Complications: Orchidis Males Oopheritis Females Pancreatitis Rubeola Measles o Paramyxovirus o Koplik spots Viral Prodrome Shows up in the cheek, buccal mucosa 1 day before rash Appearance of a gray pearl on a red base o 3 Cs Cough Coriza (thick nasal drainage) Conjunctivitis o Rash Morbilliform blotchy Appears on the head and neck proceeds down the body Disappears in the same order o Complications Otitis media Pneumonia Rapid Demyelinating disease = SSPE (rare) Subacute Sclerosing PanEncephilitis No treatment will die Present as a child with a headache who cant walk Must ask about PMH for Rubeolla Rubella = German measles o Togavirus o No 3 Cs 5

o Only a morbilliform rash after a few days after fever (rash appears like rubeola) o Warthin Finkeldey Cells multinucleated giant cells with eosinophilic cytoplasmic and nuclear inclusion bodies o Swollen lymph nodes Behind ears and neck Post-auriccular and occipital

o Complications of Rubella Neonatal rubella (pregnant mom child) If it happens in the 1st trimester one can offer an abortion b/c 70-90% of the children will be deformed Catracts Deafness Autism o Sameness o Language problems o Dont bond PDA associated because of prematurity Blueberry Muffin rash If affected after MMR vaccine child will shed virus for 2 months Varicella o Chicken pox Pox lesions come in 4 waves Red macule (red dot) Clear vesicle (dome) Pustule Scab no longer infectious 7 days to scar over Most infectious 2 days before rash breaks out 3 days after the rash breaks out Immuocompromised patients exposed to child with chicken pox must give varicella IgG within 72 hours of exposure Complications: Skin infections o S. aureus, strep. Pyogenes o Pulmonary varicella pneumonia Highly lethal Happens in adults Fifths Disease o Parvovirus B19 Erythema infectiosum (slapped face) #1 cause of Aplastic anemia Roseolla HSV VI 6

o Sixth Disease Exanthem subitum ONLY illness where rash comes 24 hrs after the fever disappears No treatment/complications HSV VII o Pityriasis rosea Circular dry patches of ski all over the body Mimics Excema X-mas tree pattern follows skin lines Herald Patch Self Limiting

Molluscum contagiosum o Poxvirus Fleshy colored papules with central umbilicus o Goes away on its own o Can be sexually transmitted Kawasaki Disease = mucocutaneous lymph node disease o Symptoms Strawberry tongue (only other is Scarlet Fever), red lips, red eyes (mucositis) Red rash all over including the Palms and Soles!!! (TRCKSSS) Swollen lymph nodes follows down the cervical chain Fever > 1020 F for at 3-5 days o Causes Vasculitis (systemic) Will cause Thrombocytoses ( platelet count) Use ASA to inhibit platelet aggregation Flu vaccine every year to prevent Reyes Syndrome (+) Heart failure o Biggest complication Will cause coronary aneurysm in 90% of cases within the 1st 6 months Do echo every month for 6 months and every 6-12 months after that If a coronary aneurysm is > 8 mm need to do bypass surgery on the child o Treatment IgG immediately block antibodies frequency of coronary aneurysm Hand and Foot Mouth o Coxsackie A o Rash = little red dots on PALMS & SOLES o Ulcers in the mouth and back of the throught Painful so wont drink and breast feed Common complication is dehydration

Lung Croup o Subepiglottic edema o Symptoms Stridor 7

 Barking cough Steeple sign on neck film o Treatment: Dexamethasone o Common causes Parainfluenza (80%) RSV (15%) Severe symptoms send to ER Influenza Adenovirus Bronchiolitis o Behaves like asthma Is not called asthma until 2 y.o. because one can outgrow bronchiolitis o Mucous collection in the small airways Recall obstructive disease o Common causes of Bronchiolitis: Parainfluenza (80%) RSV (15%) Severe symptoms send to ER Influenza Adenovirus Heart Acute Myocarditis/Pericarditis o MCC Coxsackie B o EKG Findings Myocarditis diffuse ST wave depression Pericarditis diffuse ST wave elevation (inflammation causes blood to be sent to that area leaving other areas with minimal blood flow and oxygen ISCHEMIA!!!) Recall: peri myo endo (Ishemia affects outside in) GI Gastroenteritis o Adult adenovirus o Pediatrics rotovirus GU Viral cystitis (UTI) o MCC is Adenovirus Pancreatitis o Etiology Coxsackie B Remember that the #1 cause is TRAUMA!!!

HEPATITIS Hepatitis Type Incubation Transmission A/E 2 6 weeks Fecal/Oral B DNA Segmented 2 6 months 1. IV 2. Blood 3. Sexual 4. Vertical
(mom baby

C 20 30 years 1. Blood transfusion 2. IV 3. Sexual No vertical Trans. 60% Risk

Chronic Active Hepatitis Cancer Misc

NO NO Hep E = asian version of A Known to attack pregnant women

10% Risk

Highest Risk Lower than B Dane Particle DNA If mom is +Hb-surface antigen Baby must get vaccine and IgG at birth ( remember that it takes 2 weeks for IgM to peak Full Protection Higher incidence and prevalence than C

Only after one gets B can they get D Look for a chart showing an increase of AST/ALT at 6 months after Hep B infection is getting better

Symptoms

Gastroenteritis with Shell Fish

Chronic Hepatitis Defined by: o Symptoms that are persistent o Elevated enzymes beyond 6 mos. o Persistent Hb surface antigen Deferentiate between chronic persistent and chronic active: o Liver biopsy Chronic persistent nothing wrong with the liver Chronic active will have fibrosis can lead to cancer

Hepatitis B Infection Cycle: Must have core antibody to show prior infection Surface antibody will give immunity to Hep. B Profiles to Know o + Core antibody and surface antigen Current Infection o + Core antibody by itself Window Period o + Core antibody and surface antibody Had past infection but now immune o + Surface antigen alone Just been vaccinated less than 2 weeks ago o + Surface antibody alone Vaccination

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2 mos. Hb Core = Dane Particle

4 mos.

6 mos.

8 mos.

Hbs = Surface Antigen usually positive when patient first comes in Tissue Injury

Anti-HbC = Core antibody stays for life Damage to blood vessel from Prekalikrein within Vasculitis Anti HbS = surface antibody provides immunity Window Period equivalence zone Intrinsic Pathway Kalkrein o HbE can be seen in this window Can determine infectivity XII

Extrinsic Pathway

Clotting Factors: XI

TF

VII

IX

VIII

PTT(32s)

PT(12s)

Prothrombin

Thrombin

Fibrinogen

Plasmin

Fibrin

Fibrin Stabilization Factor XIII

Fibrin Split products (D-dimers)

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General Characteristics: If you are given a Bleeding Time Think about PLATELET FXN Platelets in charge of the skin and mucosal bleeding o Skin Petichiae, Purpura, Ecchymoses o Muscosal GI, GU, Resp. Clotting Factors are in charge of controlling bleeding into cavities o Pleural o Ascities If there is an injury to collagen type IV Recall the intrinsic pathway Think about collagen diseases If Tissue Factor is being discussed Extrinsic Pathway Platelet Function: Vitamin K Dependent factors: Used for carboxylation of Release serotoin vasoconstriction blood flow these clotting factors: 1972 Release thromboxane (PGA2) promotes X o Platelet aggregation IX o Enhances vasoconstriction VII (short t , will disappear after protein C) Stimulates ADP release II o Platelet aggregation requires energy Protein C (shortest t ) Protein S Ca2+ Release stimulates Vitamin K Complex = 3rd carboxyl group Coumadin (Warfarin): Warfarin Works by inhibiting Vitamin K, o If you use Warfarin alone (-) Protein C so PT will be increased o For the next 2 days = Thrombogenic!!! Fat soluble teratogenic o Factor VII is the next to be depleted p450 dependent (WEPTD) o Protein C is a Fibrinolytic By inhibiting Protein C, will the chances of clot formation instead of preventing clots Therfore, it is better to start on heparin then later give warfarin
1/2 1/2

If a Vessel opens (break in Basment Membran Collagen Type IV) This stimulates and exposes glycoprotein IIb:IIIa o This signals the platelets into the endothelium o Hey, Platelets!!! Time to go to work Problem with signaling will cause bleeding from the mucosal surfaces 12

o Bernard Soulier Missing glycoprotein BIG platelets on blood smear o Glanzmans Thrombasthenia Defect with glycoprotein Same history but no BIG platelets Life on the Pharm: Aspirin o Blocks glycoprotein and makes it harder for platelets to anchor no platelet aggregation o Irreversible COX inhibitor non-competitive o This is the most effective way to stop platelets Useful in 1st time MI Good for 2nd time strokes, b/c 1st stroke result from scarring, 2nd stroke are due to the scar plaque rupturing Abciximib o Stops platelets from clumping o Bind to glycoprotein IIb/IIIa receptor Ticlopidine o Inhibits ADP receptors (recall that platelets need energy to do work!!) o SE: Agranulocytosis (Recall Clozapine also does this!!!) Seizures Clopidogrel o Inhibts ADP receptors blocks platelets o Clopidogrel + ASA synergistic effect Ticlopidine and Clopidogrel will not allow platelets to finish clumping affects Bleeding Time Role of Endothelium in Clotting Factor XII and XI are made in the liver Release of Factors (all made in the liver): but are NOT vitamin K dependent o V o VIII o vWF 2 Roles: Allows Factor VIII to anchor to the platelet Think about an adhesion problem Finish anchoring platelet to glycoprotein IIb/IIIa vWF Disease Factor VIII is decreased AD Bleeding time PTT Anti-cardiolipin Antibody Syndrome inhibits vWF Classic Presentation: Multiple recurrent spontaneous abortions o Hemophilia A Factor VIII deficiency X-linked recessive Recall that since this disease deals with Clotting Factors bleed into cavities!!! 13

o Treatment for vWF disease and Hemophilia A Mild Bleeding DVAPP (Desmopressin, vasopressin, mild ADH) DVAPP releases V, VIII, vWF Moderate Bleeding In vWF Cryoprecipitate which contains vWF, Factor VIII, & fibrinogen In Hemophilia A Factor VIII concentrate o High Incidence of HIV infections But it is now made synthetically Severe Bleeding Fresh Frozen Plasma contains all clotting factors o When diagnosing these clotting factor problems order a Factor VIII activity NOT a Factor VII level Need 40% activity to qualify as proper clotting Endothelium Injury o Endothelium injury stimulates tPA o tPA Activates plasminogen plasmin (fibrinolytic) D-dimers (Recall DIC Ddimers) o Urokinase o Streptokinase also binds up fibrinogen Bleeding time > tPA = BAD NEWS 20 mg IV push and drip 40 mg until clot is open Therapeutic Use: Fibrinolytics: Acute MI - Protein C & S Acute Stroke (within 3 hours) - Plasmin tPA rescue APSAC - Antithrombin III - Heparin

Inflammation o Causes the release of Kallikrein from the endothelium show up at every inflammatory response Kallikrein can activate Clotting cascasde This is the reason why DIC can be seen in inflammatory/infectious diseases And why Factor XII deficiency will not present with bleeding!!! After clot is formed o Platelets will release PDGF (+) fibroblasts to lay down new collagen o Endothelium will release EDGF (+) Type IV collagen to create new Basement Membrane o Bradykininogen is released Bradykinin Bradykinin acts as Vaso/venodilator to bring more blood ( O2) (+) ATP to form clot Bradykinin also induces itching, this why scabs are itchy and you want to pick at it!! Antithrombin III o Thrombolytic/Fibinolytic 14

o Inhibits Thrombin Affects intrinsic pathway (IX, X, XI, XII) o Measure PTT Want an INR 2-3x normal Heparin and Warfarin o Heparin Overdose Tx: IM Vitamin K (fresh frozen plasma) Heparin has a positive charge therefore, will not cross the placenta o Warfarin Overdose Tx: Protamine Sulfate o Low molecular weight Heparin 3 Benefits No need to check PTT Fewer bleeding complications Fewer cases of heparin induced Thrombocytopenia

In regards to platelet problems/pathology dont forget #1 cause of any penia is a VIRUS!!! o Next is drugs TTP vs. ITP o TTP has NEUROLOGIC CHANGES along with the Thrombocytopenia o ITP will have come after some sort of infection!!!

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