Malformation

Holoprosencephaly CHD Anencephaly, polydactyly and syndactyly Primary defect in cells or tissues that form an organ Congenital dislocation of the hip secondary to uterine constraint Clubbed feet Anomalies secondary to extrinsic mechanical forces Amniotic band syndrome Secondary breakdown of previously normal tissue or structure

Actinic keratosis Rought, scaly, erythematous papules on sun exposed areas Premalignant condition that increases the rsk of SCC Acute calculous cholecystitis Acute inflammation of the GB due to obstuion of GB neck or cystic duct MC complication of cholelithiasis, stone disrupt the protective mucus layer + prostaglandin release then ischemic disruption of the mucosal layer then BACTERILA INVASION as the last step Acute Cholecystitis Typical picture: middle aged obese female with fever and prolonged episodic right upper abdominal pain after fatty meal Acute Cholangitis Typical picture: homeless male with fever, abdominal pain and jaundice

Deformations

Disruption

Sequence

Potter syndrome leading to low volume thus fetal compression with uterus lead to flat facies, etc. Number of abnormalities resulting from a single primary defect Complete absence of an organ

Agenesis

Acute Erosive Gastritis Completely asymptomatic to UGIB Upper epigstric discomfort or pain, N/V MCC is NSAIDS and also seen in surgeries, stress ulcers, smoking and alcohol NSAID gastritis is secondary to decresed mucin and bicarbonate secretion dn epithelial cell capillary stasis Acute infective endocarditis Rapidly progressive febrile illness leading to death Risks: px with prosthetic heart valves and those who have had prior valvular inflammation and scarring MCC is Staph. Aureus adheres on damaged valves and induce tissue factor expression resulting in platelet adhesion and fibrin deposition at the site of bacterial colonization on the valve

Abdominal Aortic Aneurysm MCC is ATHEROSCLEROSIS Earliest lesion of aneurysm is: fatty streaks Micro: intimal lipid filled foam cells derived from macrophages and smooth muscle cells that engulf LDL

Acanthosis nigricans - hyperpigmented skin lesion in the axillary areas on obese - associated with Gastric CA (old) and DM (young)

Achalasia Increase in resting lower esophageal sphincter tone and diminished LES relaxation during meals Barium swallow: distended esophageal body and narrowed LES Increased risk of squamous cell CA Compare with: o Reflux adeno CA o Pill-induced esophagitis no risk of CA; usually due to tetracycline, KCL and biphosphonates

Acute interstitial Nephritis Hypersensitivity reaction 1 -2 weeks after meds like B-lactam penicillin s/sx: fever, rash, oliguria, peripheral eosinophilia, eosiphiluria (Hansel or Wright Satin) damage to the INTERSTITIUM leaving the glomeruli intact increase IgE and eosinophils Pathogenesis: IgE mediated hypersensitivity combined with cell-mediated reaction

Acute Rheumatic Carditis Micro: circumscribed interstitial collection of mononuclear inflammaroy cells with large histiocytes and prominent binuclear histiocyte Aschoff bodies, Anitschkow cells (caterpillar cells) Usually precede by Group A strep pharyngitis 10 days to 6 weeks prior Compare with o Viral myocarditis: lymphocytic interstial infiltrate with focal necrosis of myocytes o Hypersensitivity myocarditis: drugs; interstitial inflammatory with mononuclear inflammatory cells and eosinophils o Chagas disease T cruzi infection from latin America; distension of individual myobivers with intracellular trypanosomes o Diptheritic myocarditis toxin from primary focus of infection (tonsillophryngitis) in a child who has not been immunized against diphtheria; micro: pleomorphic interstitial infiltrate of macrophages without distinct aschoof body type granulomas Acute intermittent porphyria patient with bizarre symptoms like stomach pains with very mild photosensitivity, delirum, and his urine darkens in the light enzyme deficient: uroporphyrinogen 1 synthetase Porphobilinogen and aminolevulinic acid accumulate in urine Glycine and Succinyl CoA are precursors of porphrin Metallic ion is Fe!

ACUTE RADIATION SYNDROME: Radiation exposure 12 hours post-exposure: Vomiting 24 hours post-exposure: Prostration (extreme exhaustion), fever, diarrhea Later: Petechial hemorrhage, hypotension, tachycardia, profuse bloody diarrhea, maybe death. Acute Rheumatic Fever Yong with arthritis and new onset heart murmur 3 weeks after an episode of pharyngitis Group A strep usually at age 5 15 year old MITRAL STENOSIS is usually caused by FIBROSIS OF VALVE LEAFLETS Sydenhams Chorea in ARF with CNS involvement MCC of death is severe MYOCARDITIS

ADAMS-STOKES SYNDROME: Heart block, with slow or absent pulse, often accompanied by convulsions.
ADH/ Vasopressin Synthesized in paraventricular and supraoptic nuclei of the hypothalamus Increase BP by acting on V1 receptors on the blood vessel walls Please see Adrenal medulla o Produces CATHECOLAMINES - Epinephrine and NORE Pheochromocytoma o Neural crest-derived chromaffin cels episodic HPN o Eleaveted urinary hovanillic acid (HVA) and vanillylmandelic acid (VMA) o s/sx: pressure pain perspiration palpitations pallor o Rule of 10 Extre-renal Bilateral Malignant Affect children Familial o Associated with neurofibromatosis, MEN II and MEN III o Tx: phenoxybenzamine Neuroblastoma o MC in children o Amplicationo f the N-myc oncogene o Elevated HVA in urine o Patho: lobulated with areas of necrosis, hemorrhage, calcification

Acute Pancreatitis MCC are gallstones and alcoholism Duct obstruction leads to stasis of pancreatic secretion and digestion of adipose cells by lipase formation of FA that binds to Ca leading to calcium salts o ACUTE INTERSTITIAL PANCREATITIS Areas of focal necrosis and calcium precipitation Less common causes: ERCP. Drugs (azathioprine, sulfasalazine, furosemide, valproic acid), infections (mumps, measles, EBV, VZV, Coxsacke, M. Pneumoniae and M. tuberculosis), hypertriglyceridemia and structural abnormalities, surgery and hypercalcemia Ductal obstruction may cause pancreatic exocrine insufficiency o Failure to secrete adequate amylases, proteases and lipases leading to malabsorption with consequent diarrhea/steatorrhea o Weight loss and bulky, froty stools are typical clinical findings

Micro: rosette pattrn of small cells

Aging, changes Heart

Adrenal Gland CORTEX Zona glumerolosa Aldosterone Angio II, K Zona fasciculate Cortisol ACTH Zona reticularis androgens ACTH Hyperplasia of glumerulosa hyperaldosteronism Hyperplasia of fasciculate cushings syndrome Hyperplasia of reticularis adrenal hyperandrogenism hirsutism and virilisation of female and precocious puberty in male

Dec. LV size particularly at the apex to base Progressive accumulation of cytoplasmic granules lipofuscin pigment Sigmoid-shaped ventricular septum

ADRENAL DISEASES (CORTEX) Acute adrenal insufficiency/ Adrenal crisis

Rapid withdrawal of steroids Adrenal apoplexy in WATERHOUSE-FRIDERICHSEN syndrome (adrenal hemorrhage secondary to meningococcal septicaemia) Low Na, High K, low bicarbonate, low glucose Weakness, weight loss, anorexia, N/V, hypotension, SKIN PIGMENTATION (high ACTH) Pathology: bilateral atrophied adrenal glands

Primary adrenocortical insufficiency (Addisons Disease)

Alcohol Biochemical changes in the CNS Binds inhibitory GABA receptros and potentiates effects of GABA Long term causes downregulation of GABA receptors Inhibits NMDA receptors leading to upregulation of these receptors Increase synthesis of excitatory mediators in brain like NORE, serotonin and dopamine These changes lead to TOLERANCE and symptoms of WITHDRAWAL Associated with PERIVENTRICULAR HEMORRAHGE/NECROSIS esp in mamillary bodies Alcohol withdrawal Usually within 5 10 hours and reach maximal intensity in 2-3 days and subside by 4 5days Most common manifestation is SHAKES/ tremulousness Tonic clonic witin 48 hours DT or acute intoxication/fluctuant arousal level between 48 72 hours Wernicke confusion, ophtalmoplegia and ataxis Korsakoff memory loss, confabulation, personality disorder Alcoholism Can cause macrocytosis MCV > 100 maybe probably secondary to poor nutrition or direct xocitiy of alcohol on the marrow Aldolase B deficiency (AR) young person who comes in with mild tachypnia because of acidosis, he has enlarged liver, is slightly to moderately icteric; accompanying hypoglycemia (watch for seizures) Tx: terminate BOTH fructose and sucrose in the diet Alpha 1 antitrypsin deficiency Emphysema and liver disease in young, non-smoker Allergic Bronchopulmonary Aspergillosis (ABPA) ASTHMA-like (+) eosinophilia and increase in IgE and IgG to A. fumigatus Alport syndrome Nephritis + deafness and ocular manifestations EM: basement membrane splitting/disruption Inherited defect in alpha 5 chain of collage type 4 Compare with: o Membranoproliferative GN type 1

Secondary adrenocortical insufficiency (pituitary)

Low Na, High K, low chloride, metabolic acidosis ACTH is high, cortisol and ALD are low Decreased ACTH less skin pigmentation

Achondroplasia Disproportionately short arms and legs Defect of fibroblast growth factor receptor 3 Normal spine length, but have short limbs, large head and saddle nose 50% chance of transmitting the disease to his child Autoimmune hypohyphysis Sometimes seen during late or early postpartum pregnancy s/sx: HA, visual and cortical deficiency Adrenal Medullary Hyperplasia increase catecholamines

EM: basement membrane splitting Granular deposits on immunofluorescence Lobular appearance with proliferating mesangial cells and increased mesangial matrix Membranous glomeulopathy Diffuse thickening of glomerular capillary walls on ligh microscopy

judgement and lost problem-solving skills; incontinence and gait may be seen Creutzfeldt-Jakob disease

Pick bodies Rapid progressive dementia and myoclonic jerks Usually seen in corneal transplants, implantable electrodes or preparation of growth hormone Prion disease (common features are: Abnormal prion protein (PrP0 Long incubation period Spongiform encephalopathy vacuoles in the cytoplasm of the neutrophils and neurons NO inflammatory changes NO treatment Form of neurosyphilis Progressive dementia and generalized paralysis JC polyoma, seen in immunocompromised Patchesof demyelination due to infection of OLIGODENDROCYTES Progressive dementia, spasticity and seizure Linked to measles virus that persists in the CNS Micro: myelin inclusions degeneration and viral

Alzheimers disease Associated with Down Syndrome Amyloid deposits in brain tissue called AB amyloid, product of amyloid precursor protein (APP which is a normal component of neuronal membranes) o Stain with Congo red and shows aggple-green birefringence if seen under polarizedlight o Form senile plaques and neurofibrillary tangles o Deposits in vascular walls lead to amyloid angiopathy Type 4 allele of apolipoprotein E (ApoE epsilon 4) is a risk DECREASED Ach due to deficiency of CHOLINE ACETYLTRANSFERASE in hippocampus (formation of new memories) and nucleus basalis of Meynert (memory and cognition) Basa nucleus of Meynert is located at the base of forebrain and widely projects to the neocrotex Early onset Alzheimer: onset < 60, amyloid precursor protein (APP) gene on chromosome 21, Presenilin 1 gene on 14 and presenilin 2 gene on 1 these mutations lead to production of A Beta amyloid Late onset: associated with epsilon 4 allele of Apo E Other forms of dementia Vascular dementia (multi-infarct) From brain injury secondary to multiple cerebral infarcts Associated with HPN, multiple ischemic strokes and atherosclerosis NO amyloids Depression (pseudomentia) Confusion and declining mental function More rapid than Alzheimer and associated with emotional stress Picks disease Social disinhibition, speech abnormalities and emotional flattening, behavioural Note: lesions in the prefrontal cortex can abnormalities cause inappropriate behaviour, impaired Atrophy of FRONTOTEMPORAL REGIONS and

General paresis

Progressive multifocal leukoencephalopathy

SSPE

Aminoglycosides MOA: block formation of 30S initiation complex. Not for anaerobes Amyotrophic lateral sclerosis MC motor neuron disease (combined UMN and LMN disease) resulting to denervation atrophy of the muscles MCC of death is respiratory complications Macro: thin anterior roots and mild atrophy of the precentral gyrus Micro: o Loss of neurons in the anterior horn o Degeneration and atrophy of lateral corticospinal tracts o Loss of neurons in V, IX, X, XII Mutation of the gene that codes for copper-zinc superoxide dismutase (SOC1) Tx: riluzole decrease glutamate release Anaerobes Actinomyces, Bacteroides and Clostridium all lack catalase

Tx: clindamycin above diaphragm and metronidazole below the diaphragm

o o

Anal Fissure Longitudinal tear in the mucosa of the distal anal canal distal to the dentate line Majority is at the posterior midline of the anal verge due to poor perfusion Associated with constipation and low fiber diets Anovulation MCC of irregular menstruation in first 5-7 years after menarche and last ten years before menopause Antibodies SLE anti-dsDNA Drug-induced lupus anti-histone (procainamide, hydralazine, isoniazid and Dpenicillamine Sjogren syndrome anti-Ro/SSA and anti-La/SSB Antiprogestine abrotifacient RU 456 Fcn: apoptosis of endometrial cells Same function with withdrawl of presterone Anticipation Increase in severity of genetic disorders in subsequent generations - huntington and Fragile X syndrome Aortic Dissection If with history of long standing HPN, Marfans or Ehlers Danlos s/sx: severe tearing chest pain that radiates to the back

Lumbar myelomingocele (leads to leg paralysis) and hydrocephalus are almost present Compression of medulla: difficulty swallowing, dysphonia, stridor and apnea

Arterial Pathology Intimal streak

Fragmentation of elastic tissue and separation of elastic and fibromuscular components of tunica media by small cleft-like spaces Granulomatous inflammation of media Homogenous deposition of eosinophilic hyaline material in intima and media Homogenous, onion-like, concentric thickening Medial calcification/ Mockenberg medial calcific sclerosis

Initial lesion of atherosclerosis Predisposes to aneurysm rather than dissection Micro: intimal , lipid-filled foam cells from macrophages and SMC that have engulfed lipoproteins Aortic dissection

Aortic Stenosis, congenital Maybe supravalvular due to a fibrous diaphragm with small opening distal to the aortic valve Associated with Mental Retardation, peculiar facies and systolic murmur at birth th However, clinically evident at 6 decade compared to aortic stenosis which is th usually 7 decade Arnold chiari malformation Congenital underdevelopment of posterior fossa Small size of fossa causes parts of cerebellum nd medulla to herniated thorugh the formane magnum Type I o low lying cerebvellar tonsil extend below the formane magnum into vertebral canal o Asymptomatic in infants and adults with HA and cerebellar symptoms Type II o More severe and neonates present with symptoms o Abnormally formed cerebellum ndmedulla (both cerebellar vermis and medulla extend downward thorugh the formane magnum)

Segmental thrombosing vasculitis often extends into contiguous veins and nerves Segmental fibrinoid necrosis of the small vessles

Giant cell arteritis Takayasus Disease Hyaline Arteriosclerosis Non-malignant HPN or DM (diabetic microangiopathy) Hyperplastic arteriolosclerosis Malignant HPN Atherosclerosis with calcific deposits in muscular arteries Usually asymptomatic Can be seen in radiography Buergers disease Leukocytoclastic vasculitis/ microscopic polyangiitis / microscopic polyarteritis / hypersensitibity vasculitis PAN MCC of syphilis producing thoracic aortic aneurysm

Transmural inflammation f arterial wall with fibroid necrosis Vasa vasorum obliteration/endarterirtis

Luetic aneurysm may have aortic regurgitation Argyll Robertson Pupil Tx: penicillin dark field microscopy

OA

Gouty arthritis

Fibromyalgia

Septic arthritis Polymyalgia Rheumatica

Use-dependent joint pain and improves with rest Morning stiffness in < 30 minutes May have DIP swelling (heberdens) and PIP (Bouchards) due to osteophyte formation Inflammatory condition (red, swollen and painful joint Monoarticualr (first mettarsophalangeal joint) Diffuse musculoskeletal pain that worsens with weather change, stress or reduced sleep NO joint deformities Intense pain, swelling redness of joints Mostly affected are knee, hip, and shoulder Morning stiffness of neck, shoulder and pelvic girdle Weight loss, fever and increased ESR Seen in 50% of patients with temporal areritis

ARTHRITIS Ankylosing spondylitis

morning stiffness (improve with activity), myalgias and low back pain with red tinge on his left eye (+) HLA B 27 with cardiac anomalies Sacroiliac and apophyseal joints of the spine affected Involvement of CV and costosternal junctions lead to limitation of chest expansion resulting in hypoventilation (+) enthesopathies inflammation at sites of tendon insertion Systemic sign and symptoms Involved MCP and PIP - immune dx has systemic symptoms like her fever and malaise. Morning stiffness that improves with use but often lasts > 30 minutes Involves PIP and MCP and NOT DIP Triad: urethritis, conjunctivitis/uveitis and arthritis male patient comes in with myalgias and low back pain. He also has reddish (infection like) tinge on his left eye. labs came back positive for HLA B27, BUT so did chlamydia culture Case of Inability to eat dry food, such as crackers, which sticks on the roof the mouth Tongue sticking to the roof of the mouth She always has to be putting a glass of water on their bed stand to drink at night. She has difficulty speaking for long periods of time, and her eyes are dry and her right wrist is starting to hurt. Associated with hla 3 TX: PILOCARPINE At risk of lymphoproliferative disorder

Asplenic px - prone to sepsis with encapsulated bacteria S pneumonia, H. influenza and N. meningitidis

Atheroembolic disease of renal arteries Cyanotic toe + renal failure after an invasive procedure (+/-) livedo reticularis, cholesterol emboli to the retina and skin infarct Micro: neddle-shaped cholesterol crystals that partially or completely obstruct renal arterioles Atherosclerosis -fixed stenotic atheromatous lesion (lipid-filled intimal plaques that bulge into arterial lumen - lipid filled intimal plaques Atopic dermatitis Loosely termed ECZAMA Lichenified, popular, slightly scaly in the antecubital and popliteal fossa, flexor wrist, eyelids, face and around folds of neck Family hx of asthma or hay fever in the family Aggravated by excessive external irritation Dx: elevated IgE Tx: topical steroids Atrophic vaginitis Post-menopausal women and toher hypoestrogenic women s/sx: vaginal dryness, serosanguinous or water discharge and dyspareunia

Rheumatoid arthritis

Reiters (usually MALE)

Sjogrens syndrome (usually female)

Atypical depression mood reactivity, leaden fatigue (heavy arms and legs), rejection sensitivity and reversed vegetative signs (increased sleep and appetite) Tx: MAOI Autoimmune Hepatitis smooth muscle cell Ab

immynodeficiency

X linked wiskott-aldrich syndrome

His mom say he suffers often from candida. And you note he has IL-2 def, poss. eticular or ZAP-70 gene def. Your attending walks in and says he will suffer from PCP and Herpes. usually die by age 2 from PCP. You must prophylaxis with TMP-Sulfmethoxazole. Consider IV globin transfusion if counts stay low. 4 year old with recurrent otitis media, eczema, and thrombocytopenia from Strep pneumoniae. AND, he bleeds a lot. His IgM is low The key is LOW IgM, High IgA,and the bleeding. IgM response curtailed. He is not nearly as bad as SCID case, and you must give him amoxicillin (there are a lot of options here, like you can give ceftriaxone too) plus globins.

Autoimmune diseases Ataxia telangiectasia

Bruton

Chediak Higashi disease

Chronic Granulomatous Disease

Di George

Severe combined

Recurrent bronchpulmonary, bacterial, neurologic disease, thymus aplasia, telangiectasias, growth retardation, and impaired organ mutation, and is walking funny and waddling Both T and B cells are busted AFP always elevated low IgG and presents like WAS syndrome with continued bacterial infections, diarrhea. And you find out this is Xlinked too! In the absence of functional Btk , mature B cells expressing surface immunoglobulin and the marker CD19 are few to absent So similar to WAS syndrome, but WAS boys will BLEED Bacterial infections with a defect in microtubules and phagocytosis with severe gingivitis and oral mucosal ulceration + albinism Usually affected with staph and strep Tx: acyclovir then IVIg for the bacteria lymphadenopathy, hepatosplenomegaly, growth failure, and stigmata of chronic skin infections (+) Aspergillus granulomas (skin stuff) and key words phagocyte def. and Aspergillus infection Deletion of the long arm of Chromosome 22 (22q11.2 hyperreflexic on exam, has abnormal facies, congenital heart disease (TOF and interrupted aortic arch), hypocalcemia on labs, and increased susceptibility to infections. A radiograph shows he has no thymus. 3rd and 4th pouches failed to develop Young child with recurrent bacterial, fungal, infections.

Autosomal recessive PKD Presents at birth or duirn ghte first years of life with bilateral flnak masses Cyst are formed by dilated distal tubules and collecting ducts Compare with: o Multicystic kidney dysplasia multiple cysts and absence of a normal pelvocaliceal system; associated with ureteral or ureteropelvic atresia o Horseshoe kidney abnormal fusion f kidneys at poles o Potter syndrome a number of fetal renal abnormalities like bilateral renal agenesis, infantile polycystic kidney disease + Potter facies (flat nose, recessed chin, prominent epicanthal folds and lowset ears), limb defectgs and cardiovascular abnormalities

Autosomal Dominant Polycystic Kidney Disease Usually asymptomatic early in life Associated with Cerebral berry aneurysm same with Ehlers Danlos syndrome Rupture of aneurysm leads to SAH If CT is negative, LP is done and (+) if with xanthochromia (blood in CSF) IgA Deficiency recurrent bacterial sinopulmonary infections, Older with less severe disease, and complains of GI symptoms too like diarrhea. IgG and Neutrophil levels could be normal. Give antibiotics

Avascular necrosis (osteonecrosis) Due to impaired blood supply to a semeng of bone Usually ath the femoral head Associated with sickle cell disease due to occlusion, SLE due to vasculitis and steroid therpay and alcoholism Axillary nerve Injury to the surgical neck of the numerous or anterior dislocation of the shoulder Bacterial Endocarditis MCC of fatigue and new onset murmur in your Increased crea due to 50% decreased in GFR ( only if 75% of renal glomeruli is affected) Hematuria and proteinuria secondary to nephritis syndrome Maybe complicated with Acute Diffuse Prolifertive GN secondary to circulating immune complexes Bacterial Peritonitis Dull-appearing peritoneal surface with areas of viscous white-yellow supporative exudate

o Uveitis o Optic atrophy

Squamous cell CA Adeno CA

Neoplastic cells resemble normal epithelium Painless gross hematuria Grows as a papillary or sessile mass S. haematobium Glands formed by neoplastic cells

Brachial arch Brachial arch 1: loss of sensation around the jaw BRACHIAL PLEXUS Claw hand C8 T1 Bone CA Ewing Sarcoma

Undifferentiated neoplasm of neuroectodermal cells in long and flat bones of children

BARLOW SYNDROME: Floppy Mitral Valve Syndrome; Massive Mitral Valve Prolapse ------> Late apical systolic murmur, systolic click, or both.
Barrets esophagus Change of stratified squamous to columnar epithelium due to long=standing reflux disease Increased risk of adenocarcinoma Compare with: o Achalasia motility disorder due to loss of ganglion cells of LES o SCC of esophagus = risks ar smoking alcohol. Achalasia, PlummerVinson and nitrosamine-containing foods Bicornuate uterus Due to incomplete fusion of PARAMESONEPHRIC DUCTS Beckers 15 year old boy with "fatty" thick calf muscles. The child trips on a toy and strangely uses his proximal muscles to assist in standing a milder form of progressive muscular dystrophy. defective protein is DYSTROPHIN! labs show elevated CPK Tx: prednisolon

Brain tumors, Adult Glioblastoma multiforme

Meningioma

BEHCET'S SYNDROME: Vasculitis ------> secondary symptoms: o Oral and genital ulcers

From astrocytes MC primary brain tumors Found within the hemispheres (frontal or temporal or near basal ganglia) Soft and poorly defined with areas of necrosis and hemorrhage Die within 1 year Micro: pseudopalisading necrosis new vessel formation s/sx: HA, seizure, mental status change from arachnoid nd 2 MC Benign and well-circumbscribed Located on the brain surface attached to the dura, lateral and parasagittal brain, falx cerebri, olfactory grooved Micro: whorled pattern of growth with psammoma

Acoustic neuromas CNS lymphoma

Craniopharyngiomas Schwannomas

bodies (laminar calcifications) Type of schwannoma from Schwann Cells of CN VIII Found in cerebropontine angle Commonly associated with AIDS, EBV Most frequent in ummunosuppressed Micro: dense, cellular aggregates of uniform, atypical lymphoid cells Majority arises form B-cells Cells are positive for B cell markers CD20 and CD79a Located in the suprasellar region and can be calcified Visual disturbances and endocrinopathies Cerebellopontine angle Symptoms of CN VIII compression (hearing loss, tinnitus, loss of balance)

Ependymoma

ataxia; signs of increased ICP rd - 3 MC - From ependmal lining of the ventricle obstructing flow of CSF - s/sx: hydrocephalus Patho: gland-like structures called rosettes Ependymal cells from gland-like structures called rosettes th - From 4 ventricle hampering CSF flow causing hydrocephalus

Brain tumors, Children Pilocystic astrocytoma

Breast Pathology MC From astrocytes Cystic and solid mass Occur in cerebellum causing ataxia, N/V and HA due to increased ICP nd - 2 MC highly malignant - Only in cerebellum (vermis) - Solid mass s/sx: severe HA and cerebellar dysfunction Primitive neuroectodermal tumor Sheets of primitive cells with many mitotic figures (small blue cells) Homer-wright rosettes Located in cerebellum (cerebellar vermis) causing HA and gait Fibrocystic Fibroadenomas - Dense and lumpy in waxing and waning esp during menstruation - Young, usually asymptomatic - Well demarcated - Micro: cellular often myxoid stroma that encircles epithelium line glandular and cystic spaces - Benign w/in the mammary duct - MC spontaneous nipple discharge (bloody or serosanguinous) - Precancerous - Malignant clonal cell proliferation contained by the surrounding duct and basement membrane - Comedo: solid sheets of pleomorphic high grade cells with central necrosis

Medulloblastoma

Intraductal papilloma

DCIS/ Comedocarcinoma

Pagets

Sclerosing adnosis

Mammary duct ectasia

Medullary CA Phylloides tumor

- Malignant cell spread from superficial DCIS into nipple skin without crossing the BM - Unilateral erythema and scale crust - Central acinar compression and distortion and peripheral ductal dilation - Common in FIBROCYSTIC disease - Ductal dilation, inspissated but secretion and chronic granulomatous inflammation in periductal and interstitial area - Solid sheets of pleomorphic, mitotic cell with significant lymphoplasmacytic infiltrate - Similar to fibroadenoma - Increased sytological atypia and stromal overgrowth

Buergers disease Calf, hand or foot caludication Superficial nodular phlebitis with cold sensitivity Severe distal pain even at rest neural involvement Late complication: ulceratins and gangrenes of toes, feet or fingers

Carcinoid Syndrome Carcinoid tumors arises from enterochromoaffin (endocrine cells ) of intestinal mucosa If the tumor is confined in the intestine, products are metabolized in the liver thus NO clinical manifestations If the tumor is extra-intestinal (lungs) or it metastasizes in the liver, secretory products are NOT degraded thus carcinoid syndrome develops Triad of facial flusing, bronchospasm, diarrhea sec to serotonin, kallikrein, bradykinin, histamine, prostaglandins and tachykinis Hypotension is also seen Fibrous intimal thickening with endocardial plaques limited to the right heart. Degree of endocardial fibrosis correlates with plasma levels of SEROTONIN and 5HIAA ONLY RIGHT SIDE because serotonin and bradykinin are inactivated distally by pulmonary vascular endothelial MAO End result: PULMONIC STENOSIS and RESTRICTIVE CARDIOMYOPATHY Tx: OCTREOTIDE if with systemic symptoms Cardiac tamponade Fluid in pericardial space presenting with dyspnea and tachypnea (these are present if pericardial pressure >10 mmHg PE: distended neck veins, arterial hypotension, hepatomegaly, diminished heart sounds, pulsus paradoxus (drop of SBP by 20 mm/Hg or more on inspiration) NOTE: o Pulsus alterans left ventricular dysfunction o Dicrotic pulse severe systolic dysfunction o Pulsus parvus et tardus aortic stenosis o Hyperkinetic pulse fever or exercise in Normal patients or PDA or AV fistula

BROWN-SEQUARD SYNDROME: Damage (injury) to half of spinal cord ------> symptoms: o Loss of pain and temperature sensation on contralateral side of body. o Loss of proprioception and discriminatory touch on ipsilateral side of body.
Burkitts lymphoma Associated with translocation of c-myc proto-oncogene from chromosome 8 to chromosome 14 (t8,14) Primarily affects children typically with maxillary or mandibular mass Associated with EBV Micro: monomorphic, intermediate sized lymphocytes with round nuclei, multiple prominent nucleoli and vacuolated basophilic cytoplasm Starry sky patter (clear spaces that surround the macrophages

Calcium stones Low CA increases intestinal Ca absorption thus increasing Ca release from bone forming stone High protein also increased acid load stimulating Ca release from bones thus hypercalciuria High Na also increases Ca release from bone Diet for calcium stones: high Ca, low protein nd Na. Moreover, pyridoxine is patient already has Ca stones and hyperoxaluria

Cardiomyopathy Dilated cardiomyopathy

Increase in all four chambers Increased risk of mural thrombi Thinning, stretched symmetrically positioned ventricular septum Can cause CHF: ventricular dilatation, contractile dysfunction Mutations: cardiac cell cytoskeleton proteins and mitochondrial enzymes of oxidative phosphorylation

Hypertrophic (Idiopathic hypertrophic subaortic stenosis) -

Restrictive cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy -

causing defective force generation x-linked DCM: dystrophin abnormality (also seen in Duchenne and Beckers) can be from nutritional deficiencies (thiamine) or chornic anemia Asymmetricl septal hypertrophy Seen in previously asymptomatic patient with syncope provoked by exertion Septal muscle bulge into the left ventricle causing dynamic ventricular outflow tract obstruction Sudden death in athlete MCC of VF in < 30 years old Usually AD with mutations in cardiac sarcomere (beta myosin heavy chain) for myosin binding C, Trop T or tropomyosin myofibril and myocyte structural abnormality simple point missense mutation DYNAMIC LV OUTFLOW TRACT OBSTRUCTION and systolic ehection type murmur is usually seen in 25%. Obstruction is augmented when there is a decrease in LV and diastolic volume like sudden standing and valsalva Micro: myocyte hypertrophy and haphazardly arranged myocytes and myocyte bundles + prominent interstitial spaces (fibrosis) gradually worsening shortness of breath, progressive exercise intolerance, and fatigue, and swollen feet. He is an older man with amyloid deposits everywhere. PE loud diastolic S3 endocardial thickening and non-compliant ventricular walls MCC of death is CHF Mutations of Ca-binding sarcoplasmic reticulum protein

s/sx: pain and paresthesias, weakness of thumb abduction and thenar atrophy compare with: o guillain barre endoneural inflammatory infiltration with segmental demyelination o DM microangiopathy endoneural arteriole hyalinization in DM o Polymyositis endomysial inflammatory infiltration o Dermatomyositis perifascicular inflammation

CD 4 (helper T cell) Express MCH II and IL-2 CD3 is an antigen associated with T cell receptor that's why anti-CD3 Ab bind to and inhibit T-lymphocytes MONOCLONAL AB MUROMONA-CD3 (OKT3) with anti-CD3 receptro activity and used to reduce rejection with kidney, heart and liver transplants Compare with: o Anti-CD20 Ab (RITUXIMAB) inhibit B lymphocytes used to treat B cell lymphomas and RA o Anti-IgE Ab (OMALIZUMAB) for refractory moderate to severe asthma o Ati-epidermal GF receptor (EGFR) Ab (GEFITINIB, ERLOTINIB, CETUXIMAB) for non-small cell lung Ca, colon , pancreatic and SCC of head and neck o Anti-vascular endothelial GF Ab (BEVACIZUMAB) for metastatic colon Ca, mets non-small cell lung Ca, mets breast Ca, mets renal Ca and recurrent glioblastoma multiforme Celiac sprue/ Gluten Intolerance/ gluten sensitive enteropathy s/sx: malabroption, diarrhea, steatorrhea, weight loss and deficiencies of vitamins and minerals Early age or later in life chronic diarrhea and fatty stools with D xylose test (+) anti IgA Ab, B cells in the lamina propria Dermatitis herpetiformis (small vesicles on the extensor surfaces (micro: neutrophils and fibrin at tips of drmal papilla forming microabscesses Autoimmune (IgA to gliadin), also endomysial and anti-reticulin Serosa and mesentery are NORMAL micro: lymphocytic infiltrates in small intestinal mucosa and severe blunting and atrophy of small intestinal villi more pronounced in duodenum and proximal jejunum so small intestinal biopsy is confirmatory Avoid gliadin wheat in diet Compare with other malabsorption:

Maneuvers that increase venous return: squatting, sitting, supine and passive leg raising thereby increase right and left ventricular preload Sustained handgrip and Phenylephrine (selectve alpha1 agonist) increase the systemic vascular resistance and reduces the gradient across the LV outflow tract Carpal tunnel syndrome Paresthesias of thumb, index and middle fingers MCC is MEDIAN nerve compression due to chronic repretitive stress or fluid retention in RF, hypothyroidism and preganancy Also associated with DM, acromegaly and RA If with hx of chronic hemodialysis develop deposition of beta2microglobulin leading to median nerve compression

o o

Chornic pancreatitis abdominal pain, weight loss ,diarrhea; associated with chronic alcoholism, cystic fibrosis, hypertriglyceridemia Whipple disease Tropheryma whippelii; arthritis, CNS invovment Abetalipoproteinemia inherited inability to form CHYLOMICRONS; st 1 year of life, failure to thrive, progressive ataxia and abnormal RBC (acanthocytes) Chrons disease chronic inflammatory disease of the intestine; Erythema nodosum/tender SQ nodules (NOT dermatitis herpetiformis) and pyoderma gangrenosum/deep ulcers with violaceous borders

asbestos Arsenic Alkylating agents Aflatoxin B1 Atomic Bomb asbestos Aromatic amines and azo dyes Benzene Chromium and Nickel Cigarette smoking Dec fiber DES High fat diet Napthylamine/ dye workers Nickel, Cranium and Uranium nitrosamines Polycyclic aromatic hydrocarbons UV rays Vinyl Chloride/ Thorotrast

Cellular Injury Reversible: 1. 2. 3. 4. 5. Irreversible: 1.

myofibril relaxation early (first 30 minutes) ATP dec and lactate accumulation due to anaerobic glycolysis Disaggregation of polysomes dissociateionof rRNA from mRNA Disaggregationof granular and fibrillar elements of nucles Triglyceride droplet accumulation Glycogen loss Mitochondrial vacuolization (swelling on the other hand is reversible)

Bronchogenic carcinoma, mesothelioma Squamous cell Ca of skin and lung, angiosarcoma of liver Leukemia, lymphoma Hepatocellular Ca Myeloid leukemias Acute, thyroid cancer Bronchogenic carcinoma, mesothelioma Hepatocellular carcinoma Leukemia (AML) Bronchogenic carcinoma Multiple malignancies Colon Clear cell CA of daughters Breast cancer Bladder cancer Lung Ca Gastric cancer Bronchogenic carcinoma, scrotal Ca Exroderma pigmentosum basal cell and squamous cell , malignant melanoma Angiosarcoma of liver

CHINESE RESTAURANT SYNDROME: MSG reaction ------> Chest Pain, burning sensation over parts of body.
Choriocarcinoma Arise from trophoblast Can develop after molar pregnancy, abortion or normal pregnancy Baginal bleeding and mets (cough if with lung mets) Very high hCG and uterus is very big Micro: abnormal proliferation f cytotrophoblasts and syncytiotrophoblasts. NO villi Cleft lip Failure of maxillary and medial nasal pocess to fuse Closed angle glaucoma Due to impared flow of aqueous humor from the posterior to anterior chanber of the ye c-myc fcn: transcription activator Coarctation of Aorta Infantile is preductal while adult is post ductal HA and epistaxis secondary to HPN in arteries na dmuscle weakness or fatigue with exercise in lower extremities

Cerebral infarct, old Ischemic changes in the neruons release lysosomal enzymes resulting to the degradation of tissues. Phagocytes then will remove necrotic tissue leaving a cavity and astrocytes proliferate with formation of a scar called gliosis LIQUEFACTIVE NECROSIS (also seen in abscess formation) Compare with: o Caseous necrosis granulomatous reactions with mycobacterial infections; chesy surrounded by histiocytes o Coagulative necrosis relative preservation of architecture of the necrotic tissue

Charcot-Marie-Tooth disease Mutation of the genes responsible for SYNTHESIS OF MYELIN Decreased nerve conduction velocity Weakness of foot dorsiflexion due to involvement of common peroneal nerve Chemical carcinogens: Carcinogens Cancer

Colon Ca MC location is rectosigmoid followed by ascending colon If familial polyposus syndromes or with Lynch syndrome (HNPCC), site is usually MULTIPLE Left sided:obstruction, abdominal distension altered bowel habits Completely symptomatic and usually found in RECTOSIGMOID COLON followed by ASCENDING COLON May occur in multiple sites in patients with familial polyposis syndromes or with Lynch Syndrome (HNPCC) Increased CEA fcn: detect disease recurrence If left side partial obstruction change instool caliver, constipation, abdominal pain and distention, N/V If right side, FE deficiency anemia, anorexia, malaise and weight loss Usually due to ADENOMATOUS POLYPS (see adenomatous polyps) Sporadic colon adenoCA is from adenomatous polyps and secondary to adenomato-carcinoma sequence APC (chrom 5) K ras p53 DCC APC uncontrolled cell proliferation K-ras protooncogene increase in size of polyps P53 and DCC malignant transformation Adenomatous polyps Seen in > 50 years old APC gene mutation so with K-ras, p53 and DCC known as ADENOMA- TO CA SEQUENCE o APC initial appearance of small adenomatou polyps o K-ras facilitate increase of polyps size o P53 and DCC are responsible of malignant transformation f adenoma into CA COX-s inhibitor may decrease adenomatous polyp formation Types of colonic Adenomatous Polyps tubular Tubular shaped glands Smalled and pedunculated villous Villi-like projection Large and commonly sessile Velvety or cauliflower like projections s/sx: LIB leading to (+) guiac stool, microcytic hypochromic anemia, partial intestinal obstruction, secrete large amount of mucus (secretory diarrhea) and stool volume is large Increased risk to progression to ADENOCA tubulovillous Combination of the above 2

Multiple cancers is common Source: macroscopically normal areas of dysplastic mucos Mutation of DNA mismatch repair

Uncommon Adenomatous polyps

12% Dysplasia Anaplastic common CA is

Adenoma to carcinoma sequence APC Kras - p53 - DCC Note: HNPCC is also known as Lynch syndrome Colonic Polyps Non- neoplastic hyperplastic Hamartomas

Inflammatory Lymphoid

With well-differentiated mucosal cells that form glands and crypts Mucosal glands, smooth muscle and CT Peutz-jeghers syndomre or juvenile polyposis Seen in ulcerative colitis or chrons disease Found in children Consists of intestinal mucosal infiltrated with lymphocytes

Neoplastic/ Adenomatous Dysplastic mucosal cells and can transform into adenoCA Villous> tubular > 4 cm has 40% risk and < 1 cm is usually benign

Congenital bicuspid aortic valves Accelerates the normal aging process leading to premature CALCIFIC AORTIC th th STENOSIS in 6 and 7 decade. In SENILE CALCIFIC AORTIC STENOSIS usually at th th 8 -9 decades Congenital Pyloric Stenosis Male Typically with recurrent projectile nonbilious vomiting PE: visible peristalsis and presence of olive-sized mass in distal stomach or pyloric region Mass is secondary to hypertrophy of the pyloric muscularis mucosae

HNPCC-associated colon Adeno CA < 50 Right sided

Sporadic colon adenoCA >50 Left side

Colon adenoCA with UC 30 Uniformly distributed

Conns Syndrome Aldosterone secreting tumor (adenoma) leading to primary hyperaldosteronism s/sx: hypertension, hypokalemia, metabolic alkalosis and decreased plasma renin tx: surgery and medical with aldosterone antagonist (spirinolactone or eplerenone) CML

Translocation between chromosome 9 and 22. ABL ocogene from 9 is transported to BCR of chromosome 22 causing BCR-ABL which codes for Trosine kinase activity The chromosome that contains the fusion gene is called PHILADELPHIA CHROMOSOME Craniopharyngioma child with HYPOPITUITARISM compresses the optic chiasm and hypothalamus. Cri-du chat syndrome - cat cry and MR - defect: 5's short arm is deleted AND pt has cardiac defects primarily VSD and ASD Chronic Alcoholic Pancreatitis epigastic calcifications with history of alcoholism secondary to alcohol-induced protein precipitation within the pancreatic ducts causing obstruction leading to exocrine insufficiency pancreatic exocrine insufficiency will lead to malabsorption with consequent diarrhea/steatorrhea, weight loss and blukyfrothy stools MACROCYTOSIS is seen in patients with chronic alcoholism, but reversible Chronic constrictive pericarditis dense , thick fibrous tissue in pericardial space between the visceral and parietal pericardium (replacement of pericardial space by thick fibrous shell) restricts ventricular filling causing low CO and right sided heart failure resistant to medications MCC is Tuberous Caseous Pericarditis (+) Kussmauls sign paradoxical rise in height of jugular venous pressure during inspiration Chronic Mesenteric Ischemia Most often caused by atherosclerotic narrowing of the celiac trunk, SMA and IMA (look for a history of HPN, CAD, Coronary bypass surgery and carotid endarterectomy Triad: epigastric or periumbilical abdominal pain occurs 30-60 minutes after food intake, weight loss and PE is normal Angiography is the gold standard and mesenteric duplex UTZ is non-invasive alternative in assessing intestinal blood flow Its pathogenesis is similar to ANGINA PECTORIS Coronary Arteries RCA LAD

mean arterial pressure If PDA is present, decreases right to left shunting

II, III, aVF, sinus node V1, V2 V3, V4

Proximal LAD LCS

V1-V4 V5. V6, I and aVL

Inferior wall with hypotnsion and bradycardia Interventricular septum Anterior wall of left ventricle nd rd Mobitz II 2 degree and 3 degree are possible Anteroseptal transmural ischemia Lateral wall of left ventricle

Congenital QT prolongation syndrome Sudden onset syncopal episode in previously asymptomatic young Jervell and lange-nielsen syndrome (AR with deafness) Romano-ward syndrome (AD with no deafness) Both types predispose to torsade de pointe Mutation in K channel Craniopharyngioma Child (5-10) with growth retardation, HA< visual proble and hypopituitarism Arises from remnants of Rathkes pouch, outpouching of pharyngeal roof (anterior pituitary) while posterior pituitary formed from extension of hypothalamic neurons Usually with 3 components: o Tumor cells o Cysts (machinery oil liquid) o Calcified component CREST SYDNROME Calcinosis, RAynaud, Esophageal dysmotility, Sclerodactyly, TElangiectasia Accumulation f CD4 lymphocytes in skin and other tissues increased secretion f substances and stimulate fibroblast to produce collagen Excessive tissue fibrosis ensues and the HALLMARK of systemic sclerosis Creutzfeldt- Jacob disease Rapidly progressive dementia and myoclonic jerks Cryptorchidism Undescended testes Semineferous tubule is usually atrophis thus inhibin is decreased (inhibin normally inhibits FHS) thus FHS is high with low sperm count Leydig cells on the other hand are preserved thus TESTOSTERONE AND LH are normal

Churg-Strauss Syndrome PAN-associated condition with lung vaculitis, severe asthma and eosinophilia often seen in atopic patients Vascular lesion are necrotizing granulomas which causes coronary arteritis

Congenital Heart Anomalies TOF

Conunteracts cyanoitic spell by SQUATTING by increasing total systemic vascular resistan thus raising

ANABOLIC STEROIDS: will decrease LH, FSH is N and Testosterone is increased. Increase androgen suppresses LH thus testosterone is increased due to loss of inhibition.

Temporal bone fracture Between skull and dura Lucid interval followed by LOC Biconcave (lenticular) hematoma Between dura and arachnoid Gradual onset of HA and confusion Crescent shaped hematoma

Cerebral arteries MCA Arms > legs Brocas and wernickes affected if the dominant side is affected Leg> arm Urine incontinence and primitive reflexes Lateral inferior pontine Contralateral loss of pain and temperature Ipsilateral deficits in V, VIII, Horner, cerebellar symptom Lateral medullary (Wallenberg Syndrome) Contralateral loss of pain and temp Ipsilateral deficits in V, VIII XI, Horner

and posterior communicating arteries Between arachnoid and pia mater Severe HA, fever, nuchal rigidity Blood in the basal cisterns

ACA Anterior Inferior Cerebellar Artery

Associated

Charcot-bouchard HPN

Posterior Inferior cerebellar Artery

Location

CVA TIMELINE 12 24 hours 24-72 hours 3-5 days 1-2 weeks

Red neurons (eosinophilic cytoplasm, pyknotic nuclei, loss of Nissle substance) Necrosis and neutrophilic infiltration Macrophage infiltration and phagocytosis Reactive gliosis and vascular proliferation around the necrotic area Liquifactive necoriss, well demarcated soft area Glial scar Cystic areas surrounded by gliosis > 1 mos

Small arteries perfusing basal ganglia and and internal capsule Size < 1 mm Result of rupture Intracerebral hemorrahge Symptoms Sudden onset of focal deficits HPN is the most common cause of intracerebral hemorrhage

Berry (saccular) aneurysm ADPKD Marfan Ehlers-danlos Circle of willis Ant and post communicating Middle cerebral Variable 2-25 mm SAH Sudden onset of HA, no focal deficits

Subthalamic nucleus component of basal ganglia Lentiform nucleus Substantia nigra Caudate nucleus

>2 weeks

Internal capsules Thalamus

Hemibalism Wild flinging movment of extremities on onse side Wilson disease (hepatolenticular degeneration) Wing beating tremor, psycohsis, cirrhosis Parkinsons Huntington disease Chorea, dementia and behavioural abnormalities Pure motor or pure sensosry deficits Thalamic syndrome Post stroke pain burning or stabbing sensation of one half of the body

CVA Epidural Middle meningeal artery

Subdural Bridging cortical veins

Subarachnoid hemorrhage Aneurysm AV malformation of anterior

Cushing Syndrome is secondary to high CORTISOL Control of CORTISOL from CRH (hypothalamus) then ACTH (pituitary) then CORTISOL (adrenal glands)

Pituitary cushing

Increased cortisol due to High ACTH Increased cortisol after low dose dexa Decreased cortisol after high dose dexa Low ACTH NO suppression with dexamethasone High ACTH (markedly elevated)

Adrenal cushing

Ectopic cushing (small cell)

s/sx: hyperpigmentation, metabolic alkalosis, low K and high glucose Increased cortisol after low dose dexa Increased cortisol after high dose dexa Decreased cortisol after low dose dexa Differential diagnosis of cortisol excess and deficiency disorder Cortisol ACTH Primary High Low (adrenal excess) Secondary High High (pituitary excess) Primary Low High deficiency Secondary Low Low deficiency Steroid Low Low CRH Low Hyperpigmentation No -

Healthy

Low

Yes -

High High Low

Yes No No

Cystic fribrosis transmembrane conductance regulator (CFTR) is nonfunctional. Sweat chloride concentration >60 is DX. Most pronounced changes are seen in RESPIRATORY AND PANCREAS Repeated pulmonary infections: PSEUDOMONAS Since there is fat malabsorption, fat soluble vitamins are deficient. So vit K is deficient and since vit K is a cofactor for the enzyme gama-glutamil carboxylase which adds carboxyl group to glutamate residue of factor II,VII,IX & X, and protein C & S, those coagulation factors will be also deficient. Routine influenza vaccine is indicated in all CF pts, but not Pneumococcus vaccine. There is asso b/w Pseudomona pneumonia and CF, use Gentamycin+Pipercilline. Tx of an acute severe exacerbation of lung dis in CF is IV Pen/Cephalo+Gentamycin. a DELETION of a three base pair coding for Phenylalanine (DjO8) in the CFTR gene in CH7. Meconium Ileus characterized by bilious vomiting, failure to pass meconium at birth, and ground glass apperance on abdominla xray. Suspect it in a pt with Bronchiectasis(cough productive of sputum for 3 months) and Malabsorption (foul smelling stool) due to pancreatic insufficeny. One clue if the pt starts to show in his 20s is a hx of Meconium Ilueus (intestinal obstruction) as a neonate. Whenever hay acute exacerbation of pulmonary infection in a pt with CF, think Pseudomona and treat it with Pipercillin + Gentamycin. CFTR gene abnormality is a 3-base pair deletion that removes Phe at amino acid position 508 causing abnormal folding and failure of glycosylation resulting in the degradation of the CFTR integral membrane protein before it reaches the cell surface

Cystinuria Inborm defect of transporter of cystine, ornithine, arginine and lysine Found in young patients with recurrent stone formation AR Urine: hexagonal cystine crystals CVA Posterior inferior cerebellar artery stroke right sided ataxia, loss of pain temp of right face and left upper and lower extremities, hoarseness, dysphagia, loss of taste of right tongue, with vertigo and nystagmus. Anterior communicating artery stroke older male with visual field defects from a circle of willis Patient A - stroke in motor cortex that lesions UMN tract to central facial nerve PE: contralateral and lower quadrant paralysis Patient B went on a camping trip and has a lesion to the LMN CN VII bells palsy features CNS hamartomas and cardiac rhabdomyomas

Cystic Fibrosis (AR) Meconium ileus + hishsprungs , Bronchiectasis due to pseudomona and infertility and recurrent respiratory infections. Cxr showing "Tram Track pattern" and opacities

young with MR, epilepsy and facial angiofibromas. Associated cancer of the above case

Cryptococcus Px with AIDS with pulmo complications. Tissue examination shows yeast-like capsule Tx: Amphotericin B Dermatomyositis Lilar or heliotrope discoloration of the upper eyelids accompanied by periorbital edema, Gottron papules on knuckles and CK is elevated Bilateral proximal muscle weakness with difficulty climbing stairs or combing hair Perifascicular inflammation Compare with polymyositis o Endomysial inflammatory infiltration o Bilateral, symmetric weakness of proximal muscles o Reflexes are normal Duchenne and Becker muscular dystrophies Genetic error (protein dystrophin) Complete absence in Duchenne and decreased dystophin in Becker muscle dystrophy s/sx: o asymmetric weakening of paraspianl muscles hyphoscoliosis o supper weight with hand (Gowers sign) o waddlaing gait (clumsy, walks slowly) Biopsy: fibrofatty muscle replacement Manifest with proximal muscle weakness and atrophy o True hypertrophy early in the disease as distal muscles compensate for weak proximal ones then later distal extremities are replaced by fat and connective tissue (pseudohypertrophy) Developmental cardiac and/or aortic defect Down syndrome DiGeorge syndrome Friedrichs Ataxia Marfan syndrome Tuberous Sclerosis Turners syndrome DIC Diabetes Type 1 Type 2` aPTT, PT is elevated for DIC, and KEY is low platlets and POSITIVE D-Dimer test Patho: islet leukocytic infiltration Patho: islet amyoid deposition

Diabetic CNIII neuropathy usually ISCHEMIC. Somatic and parasympathetic fibers of CN III have separate blood supply thus neuropathy affects only somatic fibers leaving parasympathetic fibers intact s/sx: ptosis and down and out gaze but accommodation and pupils reponse are intact. If compression is the cause, BOTH will be affected ptosis and down and out gaze + fixed dilated pupil and NO accommodation reflex CN III neuropathy can be due to nerve compression caused by transterntorial herniation or aneurysm of POSTERIOR COMMUNICATING ARTERY Diabetic nephropathy Ovoid or spherical hyaline masses in glomerular mesangium. These nodules are eosinophilic and PAS positive and represent Kimmelsteil-Wilson disease (KW nodules) Diffuse esophageal spasm Periodic non-peristaltic esophagela muscle contractions Presents with dysphagia and chest pain Barium: corkscrew esophagus DiGeorge syndrome rd th thymic aplasia and failure of parathyroid formation sec to defect in 3 and 4 pharyngeal pouches hypocalcemic and recurrent viral and fungal infections secondary to T cell deficiency associated with TOF and aortic arch anomalies (+) chromosome 22q11.2 deletion in 90% Dissecting aortic aneurysm Severe retrosternal pain radiating to the back Initially initiated by intimal tear Major arteries maybe compressed decreaseing R arm BP blocking proximal braciocephalic trunk HPN is the most common cause Diverticulosis Abnosrmal pouches that protrude from the wall of the GIT Attributed to increased intraluminal pressure when one strains during bowel movement due to constipation thus PULSION by mechanism and FALSE by structure. CONSTIPATION is a risk factor. During adult, mechanism is above but if it happens during fetal development, it usually contains all layers Compare with TRACTION o Duet o inflammation and subseqnet scarring andare true by structure (mucosa, submucosa and muscular layers)

Endocardial cusion defects (ostium primum ASD, regurgitan AV valves) TOF and aortic arch anomalies Hypertrophic cardiomyopathy Cystic medial necrosis of the aorta Valvular obstruction due to rhabdomyomas Coarctation of Aorta

Midesophageal diverticula which occur due to mediastinal lymphadenitis and periesophageal scarring Signs of LGIB (painless) usually found in in the lower descending colon and sigmoid (all proximal to the ligament of Treitz) Tx: vasopressin

COX 1,2

Other mechanisms of different types of civerticula Traction

Due to inflammation and subsequent scarring by mechanism TRUE by structure

Down syndrome Commonly involve the heart, associated with ALL, usually treated with Thyroid hormone and AFP at 14 weeks AOG is low Dystrophic calcification Hallmark of cell injury and necrosis MC sites are aged or damged valve or atheromatous plaques Eating Disorder Anorexia Decreased LH, FSH, estradiol and estrone secondary to decreased body fat leading to lost of LH surge and decrased gonadotropin (HYPOGONADOTROPHIC AMENORRHEA) Amenorrhea is sec to loss of pulsatile GnRH form hypothalamus due to decreased body fat. (same distance with long distance runner, ballet dancers). If untreated, decreased estrogen can lead to OSTEOPOROSIS EBV fever, hepatosplenomegaly, lymphadenopathy and + heterophil Ab test. herpes virus, DS linear enveloped Folic Acid Function: Methylation reactions ...

PGD2, E2 and F2 Vasodilation and edema PGI2 (prostacyclin) Vasodilation and inhbits platelet aggregation TxA2 Vasoconstric and promote platelet aggregation 5-lipoxygenase Leukotrienes 5-HETE and L B4 Chemotaxis L C4, LD4 and LE4 Vasoconstriction, bronchospasm and increased vascular permeability 12-lipoxygenase Lipoxins Lipoxin A4 and B4 Vasodilation Inhibition of neutrophil chemotaxis Stimulation of monocyte adhesion Note: LB4 stimulates neutrophil migration. Other chemotactic agents are 5-HETE and C5a

Prostaglandins Thromboxanes

Ehlers Danlos Syndrome Skin perextensibility, joint hypermobility, tissue fragility, poor wound healing and easy bruising

EISENMENGER'S SYNDROME: VentricularSeptal Defect ------> Pulmonary hypertension and cyanosis.

Eicosanoids enzymes

Main products of arachindomic acid metabolism Group of compound Examples and functions

Endocarditis, bacterial S. aureus or S. viridians, RF or SLE (Libman-Sacks endocarditis) or other processes like malignancy Right sided endocarditis IV drugs S. aureus

SBE after tooth extraction S. viridians Endocarditis caused by Strep bovis is associated with colonic CA

Endocarditis, Non-bacterial thrombotic (NCTE) Small sterile non-destructive fibrinous vegetations along lines of closure of cusps Micro: vegetatiosn are bland thrombus without inflammation or valvular damage secondary to hypercoagulable state (maybe due to CA like mucinous adenoCA of pancreas , adenoCA of lungs) If NBTE is associated with disseminated CA, called MARANTIC ENDOCARDITIS Same mechanism with TROUSSEAU SYNDROME /migratory thrombophlebitis seen in disseminated CA Endometrial Pathology Endometriosis - Endometrium outside the uterus mostly in ovaries (endometrioma/ chocolate cyst) - Nodularity of uterosacral ligaments and fixed retroversionof the uterus - Dysmenorrhea, dyspareunia, dyschezia, infertility Endometrial - Prolonged exposure to estrogen Hyperplasia - Associated with PCOS< estrogen-producing tumors (granulose cell tumor) and HRT - Vaginal bleeding Carcinosarcoma - Maliganant mixed mullerian tumors - Epitjelial (endometrial-type glands and mesenchymal Erosions Mucosal defect that does not penetrate the muscularis mucosa Seen in acute erosive gastritis caused by NSAIDS, surgery, Cushing ulcer, burns, smoking and alcohol

Present with oliguira, anorexia and flank pain within 24-72 hours after ingestion High anion-gap metabolic acidosis and osmolar gap are typical Micro: ballooning and vacuolar degeneration in proximal convoluted tubles

EYE PROBLEMS Central Retinal Artery Occlusion

Diabetic Retinopathy

Amaurosis Fugax

- acute painless monocular vision loss - c entire visual field and often permanent - pale retina and cherry red macula - central retinal artery is a branch of ophthalmic artery and from internal carotid artery Predisposing Factors: AF and carotid artery stenosis - blurry vision, poor night vision, floater, decrease peripheral vision Findings: cotton wool, new retinal vessel - painloess transient monocular vision loss secondary to embolus in the ophthalmic artery does not last more than a few seconds Contralaeral upper quandrantanopia (pie in the sky)

Temporal Lobe infarct involving Meyers Loop

ACCOMODATION (NEAR REFLEX) Change in optical power of the eye to maintain focused image on the retina o Near object: ciliary muscle contraction causes relaxation of zonular fibers allowing lens to relax and assume a convex shape o Distant object: ciliary muscles relax and lens flatten due to outward radial tension exerted by zonular fibers o With age: stgroma of lens sclerotic leading to decreased lens elasticity

Esophageal CA Incidence of SCC = incidence of AdenoCA SCC o Solid nests of neoplastic squmaous cells with abundant eosinophilc cytoplasm and distainct borders o Important risk factsrs are alcohol and tobacco o Plummer- Vinson, achalasia and corrosive stricture are prone for SCC o s/sx: progressive dysphagia first to solid then both solid and liquid leading to food retention, dilatation of esopohageal body and symptoms of intermittent non-progressive dysphagia o Ethylene glycol Found in automobile antifreeze, engine coolants and hydraulic brake fluids Metabolized to glycolic acid and to oxaliacid precipitating to calcium oxalate crystals