UL exam review

ACE inhibitors

"-pril"—eg, benazepril, captopril, enalapril, lisinopril, ramipril Mechanism: inhibits the conversion of angiotensin I to angiotensin II Normally, ACE breaks down *bradykinin* (which is a *vasodilator*) ∴ ACE inhibitors will *increase bradykinin* levels, this causing *further vasodilation*.

ARBs- (angiotensin II receptor blockers)

"-sartan"—eg, azilsartan, candesartan, eprosartan, irbesartan, losartan, valsartan Mechanism: block the activation of angiotensin II receptors Angiotensin II receptor inhibitors are not associated with a cough side effect because they do not affect the metabolism of bradykinin by ACE. So ARbs are a recommended alternative for patients who develop an ACE inhibitor-associated cough. Side effects: - Hyperkalemia - Crosses placenta, teratogenic

Cardinal signs of inflammation

"Pain, swelling, redness, heat, loss of function" Rubor (redness due to vasodilation of ARTERIOLES and thus increased blood flow)... mediated by histamine (most impt), bradykinin, prostaglandins I2, D2, E2 Calor (heat due to increased blood flow via mediators above) Tumor (swelling @ post capillary venule due to extravascular accumulation of fluid, due to histamine and blood vessel damage) Dolor (pain due to increased pressure exerted by the accumulation of interstitial fluid and to mediators such as bradykinin and prostaglandins PGI2, PGE1, and PGE2) Function laesa (loss of function)

Bisphosphonates

"dronates"... bind hydroxyapatite on bone, prevent demineralization by inhibiting osteoclast differentiation and induce their apoptosis

Macrophages

"immune system's sentinels", found just below the surface of all areas of your body which are exposed to the outside world - areas that are prime targets for microbial infection. Exist in 3 states: 'resting', 'primed', 'hyperactive'. Resting, just clean up 'debris' from dying cells. Primed, express MHC-II with signal from INF-y. Hyperactivated macrophages receive signals from pathogen such as mannose or LPS, grow larger and enhance phagocytosis. Hyperactivated macrophages also produce and secrete TNF, which can kill tumor cells and virus infected cells, and can help activate other immune system warriors. Digested material in a phagosome is fused to a lysosome → phagolysosome Plays a key role in atheroma formation Epithelioid macrophages are the principal constituent of granulomas

Rb

'Rb protein is a *tumor supressor* gene which normally is *bound to E2F*. Transition from G1 to S *can only happen* when* transcription factor E2F* is unbound from Rb, and is *free in the nucleus*. *cyclins*, such as *cyclin D1* function as regulators of CDKs (Cyclin-dependent kinases). Cyclin D1 binds to CDK4 OR CDK6, and forms a *cyclinD1-CDK 4or6 complex*, and this complex *inhibiting the tumor supressive activity of Rb*. It does this *phosphorlation of Rb* by the *CyclinD1-CDK 4or6 complex*, and forming *phosphorylated Rb (P-Rb)* *Phosphorylated Rb* is no longer able to hold the *transcription factor* called *E2F. E2F is released, makes it 'free', and allows cell to progress from *G1--> S phase.* *mutated* Rb causes an overexpression of CDK4&CDK6 or cyclin D1, causing excess phosphorylation of Rb, excess release of E2F, and thus the cell is *NOT* arrested in the checkpoint after G1 and before S. Note: since Rb is a *tumor supressor gene*, BOTH copies must be knocked out.

test and confirm SLE

(1) Serum ANA is the best screening test for SLE (sensitivity 99%). (2) Specificity for anti-dsDNA is 99% and 100% for anti-Sm. (Smith) Confirm SLE: anti-dsDNA and anti-Sm antibodies Antiphospholipid antibodies (1) Lupus anticoagulant and anticardiolipin antibodies

Three mechanisms reduce blood loss:

(1) vascular spasm, (2) platelet plug formation, and (3) blood clotting (coagulation). Vascular Spasm When arteries or arterioles are damaged, the circularly arranged smooth muscle in their walls contracts immediately, a reaction called vascular spasm

complications of dilated cardiomyopathy

*Biventricular* dilated cardiomyopathy leads to an inability to move fluids throughout the body accordingly and to maintain proper pressures, manifesting as *pleural effusions and edema*. Other Complications include *mitral* and *tricuspid* valve regurgitation... also arrhythmia. Also Dilatation of cardiac tissue disrupts the electrical conduction system, leading to left and/or right *bundle branch blockages*, and often presents as atrial and ventricular *arrhythmias*.

Quick Review of B12/Folate Metabolism:

*Folate is obtained via green vegetables, and fruits, absorbed in the jejunum (!!!!). The enzyme intestinal conjugase (which is inhibited by phenytoin) is required for absorption. *Vitamin B12 is absorbed in the terminal ileum. B12 absorption is slightly more complicated: -B12 is bound by R-factor which protects it from gastric acidity!! -In the duodenum, pancreatic enzymes hydrolyze the R-factor bond and B12 is bound by IF (which is synthesized by gastric parietal cells!! ). -The B12-IF complex is absorbed in the terminal ileum. *Folate and B12 are required for the synthesis of dTMP.

FAP is associated with what else?

*Gardner syndrome*- FAP + osteomas (benign tumor of bone) of the mandible and skull, as well as epidermal cysts and thyroid tumors. *Turcot syndrome*: FAP + CNS tumors (particularly medulloblastoma and glial tumors)

2nd most common colorectal cancer pathway

*HNPCC* (Lynch syndrome): MMR/microsatellite instability pathway is second Micosattellites are non-coding sequences of DNA, they are copied every time with DNA replication.... but if there is a *defect* with *mismatch repair (MMR) genes* (genes which correct point mutations or small insert/deletion loops) such as: - MSH2* on *chromosome 2p* -- *MLH1* on *chromosome 3p* • MSH2 forms dimer that recognizes the mismatched base on the daughter strand and binds the mutated DNA. It also recruits MLH1. MLH1- - Cuts daughter strands and recruits DNA helicase II to unwind the 2 strands and recruits endonucleas to remove mismatched DNA. A defect in these MMR genes leads to *microsatellite instability*. This result in the accumulation of mutations in microsatellites, predisposing to carcinogenesis. This is a sign that other genes are unstable, and leads to risk of Colorectal, ovarian and endometrial carcinoma. These cancers usually arise *de novo* (not from a precursor adenoma) at relatively early age, and *usually* right sides (!!)

Acute tubular necrosis

*Injury and necrosis* of *tubular epithelial cells*, and is the *most common cause of acute renal failure*. Can be caused by either: 1) *ischemic* or 2) *nephrotoxic* insult. results in necrotic cells that slough off and plug the tubules, which obstructs and results in a *backpressure* which *decreases GFR*, causing intrarenal azotemia. As the epithelial cells die, they come into tubule and get *casted* in the shape of it, so they come out in urine as *brown, granular casts*

Idiopathic Pulmonary Fibrosis:

*Interstitial fibrosis* due to idiopathic alveolar inflammation. It is Cytokine mediated, mostly in male smokers between 40 and 70. You get *cyclical lung injury* and *TGF-B* from injured pneumocytes release it and induce fibrosis. Repeated epithelial injury → abnormal repair and fibrotic changes.

Musosal/submucosal infarction in ischemic bowel disease

*Mucosal* and *mural infarctions* are generally due to some *degree of hypoperfusion/hypotension*. Mucosal and mural infarcts: Hemorrhage, ulceration and necrosis of the mucosa but relative sparing of the serosa. Mucosal or mural infarctions can occur anywhere from the stomach to the anus.

Rheumatic fever and heart

*Pancarditis* (inflammation of the entire heart) of rheumatic fever refers to endocarditis, myocarditis (leading to early death from heart failure), and pericarditis with pericardial effusions. Endocarditis: high pressure valves are most affected, forming tiny vegetations. Frequency of valves affected is *mitral > aortic >> tricuspid* Myocarditis: *Aschoff bodies* within myocardium formed. These are characterized by chronic inflammation, with *Anitschkow cells* (!!!). These are activated histiocytes with a rod shaped "caterpillar", slender wavy nucleus. Note: Myocarditis is most common cause of acute RF death, and myocarditis is characterized by *Aschoff bodies* with *Anitschkow cells*! There is also *pericarditis* which leads to a friction rub.

Transmural infarctions in Ischemic bowel disease

*Transmural infarctions* are generally due to: 1) acute *vascular obstruction of SMA* due to *atherosclerosis, aortic aneurysms, or embolism (maybe a-fib?)* 2) thrombosis of *mesenteric vein*, seen in *polycythemia vera* Intestinal segments at the *ends of their arterial supplies* are *most vulnerable to ischemia *"" these are called *watershed zones* The two most commonly affected watershed zones are: 1) the splenic flexure 2) the sigmoid colon. Watershed zone infarctions are most common in transmural infarctions.

AAA and its cause

*balloon-like dilation* of the *abdominal aorta*, usually arises *below the renal arteries* but *above the aortic bifurcation* (!!!) Abdominal aortic aneurysms are most commonly caused by *atherosclerosis* and are usually seen in *hypertensive male smokers* older than *60 years* of age. Atherosclerosis *increases the diffusion barrier* from the lumen, to the media creating *atrophy and weakness* in the vessel wall. *Below the renal arteries* there are *no vasa vasorum!!!* ; therefore, the aorta *must rely on diffusion* for getting oxygen and nutrients.

Hyaline arterio*lo*sclerosis

*chronic HTN* and/or *diabetes mellitus* (!!!!!!!!!!!) leads to endothelial injury, and plasma proteins leak into the walls of small arteries and arterioles, causing smooth muscle cells increase matrix synthesis and thicken. Results in reduced vessel caliber with *end-organ ischemia*, with *renal vasculature* especially prone to *glomerular scarring* (arterio*lo*-nephrosclerosis)...., which is the reason diabetics and hypertensives get chronic renal failure!!! Kidney scars, shrinks.

Zenker's diverticulum

*false, esophageal* diverticulum, due to esophageal dysmotility causing ↑ esophageal pressure.... caused the diverticula through a defect in muscular wall. Usually occurs above upper esophageal sphincter, at junction of esophagus and pharynx. S/Sx: halitosis (food sticks in the diverticulum), dysphagia/obstruction (Sx of root cause)

Protection of stomach

*foveolar cells* are mucus-producing cells which cover the inside of the stomach, protecting it from the corrosive nature of gastric acid. Also secretes bicarbonate. normal blood supply provides nutrients to the mucosa, and can sweep away some acid.

Chronic renal failure

*irreversible loss of nephrons* which leads to ↑ glomerular capillary pressure in remaining nephrons. This causes *hyperfiltration damage* , ultimately forming fibrosis, scarring, *loss of additional nephrons* Leads to *shrunken kidneys*.... also those on dialysis have *increased risk of renal cell carcinoma*

H-pylori

*microaerophilic, gram negative, urease-positive, spiral-shaped bacillus* !!! can cause gastritis, peptic ulcers (infects stomach and duodenum) and, if untreated, gastric cancer (both adenocarcinoma and MALT). Serum IgG may be elevated to fight the infection. The patient may present with unexplained iron deficiency anemia (from a bleeding ulcer) or unexplained vitamin B12 deficiency, because gastric parietal cells cannot produce enough intrinsic factor necessary for B12 uptake.

Asthma

*obstructive* lung disease characterized by hyperreactivity of the airways causing *reversible* obstruction and *chronic inflammation*.

Clinical features of ATN

*oliguria* with *brown, granular casts* - elevated BUN and creatinine - hyperkalemia (decreased renal excretion of potassium) with metabolic acidosis (decreased excretion of organic acids) Hyperuremia can result in altered mental status.

Mitral Valve prolapse

*prolapse* of the mitral valve into the *left atrium* during *systole*, and results from excess mitral valve leaflet tissue or myxomatous degeneration of the valve or the chordae tendineae. Etiology not fully known, but it is associated with genetic disorders: Marfan's syndrome, Ehlers-Danlos syndrome, and autosomal dominant polycystic kidney disease The majority of patients are asymptomatic. Otherwise the most common presenting symptoms are palpitations and chest pain.

Mechanisms of autoimmunity

*release of sequestered antigens* Tissue antigens that are sequestered from the circulation are not seen and therefore self tolerance to these antigens is not induced. ie, *myelinbasic protein *which is sequestered by the blood-brain barrier. When an injury or trauma to tissues occurs following a bacterial or viral infection, it appears in blood. *molecular mimicry*- Where a viral, bacterial, or other foreign antigen bears epitopes with amino acid sequence homology to a normal host protein. *modified self hypothesis* This suggests that autoimmunity may arise as a result of immune response against modified self-determinants.

Ulcerative colitis

- Autoimmune etiology - Mucosal/submucosal inflammation - *Rectum/colon* (starts in rectum and moved up to *cecum* at furthest) - "lead pipe" appearance - SMOKING decreases risk - Crypt abscesses (!!!!) (neutrophils in cypts).. ulcers, bleeding/bloody diarrhea, NO granulomas (Th2) mediated - psudopolyps (!!) - risk for CR cancer !!!! (risk is based on *duration of disease* and *extent of involvement*) - Toxic Megacolon risk (could rupture( - LEFT lower quadrant pain

Minor Jones criteria:

- Fever - Arthralgia (however, arthralgia cannot be used as a minor criteria if polyarthritis is counted as a major criteria) - ↑ serum levels of acute phase reactants (eg, CRP, ESR) - Prolonged PR interval on EKG

latent viral infections

- HSV-1: Latent in trigeminal nerve ganglion - HSV-2: Latent in sacral nerve ganglia - VZV: Latent in any sensory ganglia - EBV: Latent in B-cells - CMV: Latent in leukocytes

Pre-eclampsia

- Hypertension (increased vasoconstrictors) • Ranges from just below 140/90 mm Hg to >160/110 mm Hg, 6 hours apart, 1 week period - Proteinuria in nephrotic range (>3.5 g/24 hours) • Usually >5 g/24 hour urine collection - Dependent pitting edema • Due to loss of albumin in the urine

Diagnose celiac

- IgA or IgG antibodies to deamidated gliadin. - Antiendomysial IgA antibodies - Celiac patients are more likely to be IgA deficient, so important to test for IgG

types of vaccines

- Live, attenuated vaccines - Inactivated vaccines - Subunit vaccines - Toxoid vaccines - Conjugate vaccines

Osteitis Fibrosa Cystica

- Loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue (peritrabecular fibrosis), and the formation of cyst-like brown tumors in and around the bone - hallmark of severe hyperparathyroidism. Radiograph showing "salt and pepper" pattern of irregular lucencies in the skull of a patient with chronic renal failure

- Pegylated IFNa-

- Pegylated IFNa- PEG is added to make interferon last longer in the body. Interferons (IFNs) are proteins made and released by host cells in response to the presence of pathogens such as viruses, bacteria, parasites or tumor cells. They allow for communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.

Types of hypothyroidism and TSH

- Primary hypothyroidism (caused by thyroid hypofunction): ↑ serum TSH - Secondary hypothyroidism (caused by pituitary hypofunction): ↓ serum TSH - Tertiary hypothyroidism (caused by hypothalamic hypofunction): ↓ serum TSH When hypothyroidism is clinically suspected, serum TSH is usually the most sensitive test. ↓ Total T4 and free T4 ↓ T3 resin uptake.

hormones during menopause

- Sensitivity of the follicles towards FSH decreases with age. - Probably due to a decrease in secretion of inhibin (produced by the granulosa cells in the follicles). - The first change and therefore first indicator of menopause is a rise in serum FSH levels. - This occurs 4-5 years before the cessation of the menstrual cycles. - Estrone does not alter because it is mainly produced by peripheral conversion in the fat from androstenedione secreted by the adrenals, while oestradiol is of ovarian origin. - estrone is the main circulating oestrogen after the menopause, and although it has a weak action, concentrations may be sufficient to prevent the symptoms of oestrogen deficiency, especially in fatter woman.

HCV and carrier

- Up to 85% of adults can be chronic carrier - Virus mutates a lot. RNA virus, so RNA polymerase has no proofreading, leads to variable genome. -selective pressure from the host, mutations takes place in the E2/E1 proteins -high rate of viral replication results in an increased level of viral heterogeneity, which allows the virus to evade the host immune response.

Kidneys with age

- decreased size, number of glomeruli decrease - impaired response to stress and homeostasis management - GFR decreases - decreased ability to concentrate urine

Excess corticosteroids and Cushings

- leads to bilateral adrenal atrophy due to negative feedback by steroids shutting down ACTH

S: Sx of hyperthyroidism

- ↑ O2 consumption → ↑ RR (tachypnea) - Weight loss despite ↑ appetite - heat intolerance - - ↑ Synthesis of cardiac β1 receptors → - ↑ HR (sinus tachycardia) - ↑ contractility → ↑ SV (stroke volume) ∴ ↑ PP (pulse pressure) - ↑ HR and ↑ SV → ↑ CO (cardiac output) → cardiomegaly, systolic hypertension, high-output heart failure • Nervous System: Increased sympathetic nervous system tone → - Fine tremor (eg, of the hands) - Anxiety - Insomnia - Emotional lability - Inability to concentrate - Brisk DTRs (deep tendon reflexes) • Ophthalmologic: - ↑ SNS → overstimulation of levator palpebrae superioris (a muscle which receives SNS innervation from the internal carotid plexus & contracts reflexively to elevate the upper eyelid) → wide-eyed staring gaze and lid lag - Note: true thyroid ophthalmopathy with exophthalmos (proptosis) is only seen in Graves disease • Gastrointestinal: - Increased GI motility → malabsorption → diarrhea • Endocrine: - ↑ Bone turnover → osteoporosis → ↑ risk of fractures - Oligomenorrhea

airway problems in burns

-Airway: intubation (eg. inhalation) and or escharotomy • Causes for resp problems - edema compressing breathing II. CO poisoning: 100% O2 by facemask III. Smoke inhalation pulmonary injury: intubate

Thyroid hormone synthesis

-Cell converts tyrosine into thyroglobin and pushes thyroglobin into follicular lumen - iodine brought into cell (via Na+/I- symporter) - pushes into follicular lumen where it is oxidized to I2 by *thyroid peroxidase), this immediately reacts with tyrosine molecules in the *thyroglobulin*, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). DIT + DIT = T4 DIT + MIT=T3 Upon stimulation by TSH, follicular cells endocytoses thyroglobulin and lysosomal enzymes digest thyroglobulin, releasing T3 and T4 into the circulation.

Clinical features of pneumonia

-Fever/chills as bacteria gets into blood. -Cough with yellow-green (pus) or rusty sputum (blood) - Tachypnea with pleuritic chest pain (arises when you breathe in and stretch pleura). - Decreased breath sounds with dullness to percussion - Elevated WBC

Vitamin D deficiency

-Lack of sun exposure - poor diet - malabsorption - liver 25-hydroxylation impairment (converts vitamin D into 25-hydroxyvitamin D (calcidiol), which is the major circulatory form of the vitamin. - impaired Kidney 1α-hydroxylation (converts calcidiol into calcitriol, which is main active form)

Lobar pneumonia

-characterized by *dense consolidation* of an *entire lobe* of a lung. May involve be one one lobe, or can even entire lung. Bacteria *Streptococcus pneumoniae* is the most common community acquired pathogen....

Burn management first degree

-first degree: topical creams (pain), oral NSAIDs -second degree (superficial): daily dressing changes w topical antibiotics, polysporin, leave blisters intact unless circulation impaired

categories of oncogenes

-growth factors - growth factor receptors - signal transducers - cell cycle regulators

hepatitis treatments

-liver transplant in extreme cases - Pegylated IFNa- -Entecavir (Hep B mostly) - Ribavirin (Hep C mostly)

Causes of Maldigestion

-pancreatic diseases - bile salt deficiency - enzyme deficiency (ie, lactase

4 phases of lobar pnemonia!! *

1) Congestion 2) red hepatization 3) grey hepatization 4) resolution

phases of Hep B

1) Early 2) acute infection 3) 'window' phase 4) Recovered phase 5) Immunized 6) Healthy carrier 7) Infective carrier

causes of Cushings (4)

1) Excess corticosteroids 2) Primary adrenal adenoma, hyperplasia, carcinoma (one adrenal is big, opposite adrenal is small) 3) ACTH secreting pituitary adenoma (both adrenals are big)- Cushing DISEASE!!! 4) Paraneoplastic ACTH secretion (usually small cell lung carcinoma, both adrenals are big)

causes of intrarenal AKI

1) Glomerular disease—acute glomerulonephritis, usually due to RPGN (rapidly proliferative glomerulonephritis): - 2) Tubulointerstitial disease: - ATN (Acute tubular necrosis): Can be caused by ischemic or nephrotoxic insult. Ischemic ATN is the most common cause of AKI. - Drug-induced interstitial nephritis 3) Vascular disease: - Intrarenal vascular occlusion— - Intrarenal vasculitis—eg, Wegener granulomatosis

Hep B serology markers (5)

1) Hep B Surface Antigen (HBsAG) 2) Hep B e-antigen (HBeAG) and HBV-DNA 3) Anti HBV core antibody IgM (anti-HBc IgM) 4) Anti HBV core antibody IgG (anti-HBc IgG) 5) Anti HB's

causes of pre-renal AKI

1) Hypovolemia: - dehydration, inadequate oral fluid intake - hemorrhage, burns - vomiting, diarrhea, excessive use of diuretics 2) Hypotension: - cardiogenic shock (eg, myocardial infarction) - massive peripheral vasodilation: - septic shock (eg, gram-negative -sepsis due to UTI), - neurogenic shock (eg, spinal cord injury), - anaphylactic shock (eg, bee sting) 3) Low cardiac output: - CHF (congestive heart failure) - constrictive pericarditis - coarctation of aorta (decreased cardiac output to lower extremities, including the kidneys) 4) Hypoalbuminemia: - cirrhosis - nephrotic syndrome - burns - malabsorption 5) Renal artery stenosis

Only three pathologic processes affect frequently the prostate:

1) Inflammation (acute/chronic prostatitis) 2) Benign nodular enlargement 3) Tumors- usually *acinar type*.

Neutrophil arrival and function steps

1) Margination 2) Rolling 3) Adhesion 4) Tight binding 5) diapedesis (Transmigration) 6)chemotaxis) 7) Phagocytosis 8) Destruction of phagocytosed material

2 mechanisms of diabetes complications

1) Non-enzymatic glycosylation (NEG) of vascular basement membrane ("sticking" sugar on vascular basement membrane). 2) osmotic damage

Types of nephritic syndrome

1) PSGN (poststreptococcal glomerulonephritis) 2) RPGN (rapidly progressive glomerulonephritis) 3) Goodpasture syndrome 4) IgA nephropathy

fermin layers

1) Papillary layer - loose connective tissue 2) Reticular leyer - irregular, dense connective tissue

Spontaneous PTX

1) Primary spontaneous PTX: Occurs in people with no underlying lung disease and in the absence of a traumatic event. The typical patient is a tall and young male and commonly has *asymptomatic blebs* or bullae. 2)Secondary spontaneous PTX: Occurs in individuals with underlying lung pathology, most commonly COPD. trachea shifts *toward* the affected side. Spontaneous PTX can be treated with chest tube drainage.

neurulation forms 3 major things:

1) The neural tube, which gives rise the central nervous system. 2) The neural crest, which migrates away from the dorsal surface of the neural tube, and gives rise to : -Melanocytes -pia matter, arachnoid matter - Nerve cells and glia - Vascular plexus and intestinal nerve network - Chromaffin cells of the adrenal medulla 3) The epidermis, which covers over the neural tube once it is created.

JGA secretes renin when

1) beta adrenergic stimulation 2) decreased renal perfusion pressure due to decreased blood pressure 3) low NaCl in macula densa

4 glands in stomach

1) chief cells 2) parietal cells 3) foveolar cells 4) enteroendocrine cells

4 types of skin cells

1) keratinocytes- confer strength, rigidity 2) melanocytes- production of melanin, located in *stratum basale* 3) Langerhans cell- located in *stratum spinosum*, they are APC dentrittic cells 4) merkel cell- unclear function, may be mechanoreceptor or neuroendocrine... typically in thick skin

3 patterns of pneumonia

1) lobar pneumonia 2) bronchopneumonia 3) interstitial pneumonia

multple myeloma and kidney conditions

1) metastatic calcification secondary to hypercalcemia 2) pyelonephritis b/c of increased infection 3) AL amyloid deposition

3 immediate causes of MI

1) obstructive intracoronary thrombus 2) vasospasm 3) emboli

Disrupted systems by carcinogenic agents

1) proto-oncogenes 2) tumor suppressor genes 3) regulators of apoptosis

Obstructive lung disease spirometry !!

1) ↓ or normal FVC 2) ↓↓ FEV1 3) ↓ FEV1/FVC ratio (Normal 80%... so in obstructive it is <80%) 4) ↑ RV

3 types of asthma

1. Atopic asthma- is the most common form. It represents a classic form of *type I hypersensitivity* 2. Non Atopic asthma- characterized by a *lack* of allergen sensitivity. Airway reactivity classically occurs in response to *viral infections*. 3. Drug induced - asthma is due to the effect of *NSAIDs*, which *block the COX* pathway leaving the *unopposed lipoxygenase pathway* which produces *leukotrienes* (potent bronchoconstrictors).

shapes of neurons

1. Bipolar Two processes extending from the cell body 2. Pseudopolar- One long dendrite coming in from the body periphery and an axon which course to the dorsal root, into the spinal cord 3) multipolar- More than two processes extending from the cell body. However, each neuron has only one axon

Major subtypes of emphysema (!!)

1. Centri-acinar (Centrilobular) (most common) 2. Pan-acinar (Panlobular) 3) Paraseptal (Distal Acinar) Centriacinar- involves acinus (Upper lobe) with *sparing of distal alveoli*. think *centriacinar, cigarretes*, because it is so associated with *smoking*!! Panacinar- involves lower lobes. Associated with *alpha 1 antitrypsin* Paraseptal- proximal portion of the acinus is normal, and the distal part is predominantly involved. Occurs adjacent to areas of fibrosis or atelectasis.

complement pathways

1. Classical (antibody) 2. Alternative 3. Lecitin All activate C3. Once activated, C3 begins a cascade of reactions that brings about phagocytosis, cytolysis, and inflammation.

Mechanisms of metastasis

1. Downregulation of E-Cadherin (cadherins keep cells attached to one another). 2. Tumor cell can then attach to lamenin in basement membrane, produce collagenase to degrade collagen type 4. 3. Attach to fibronectin in ECM and spread locally, then enter vascular or lymph.

Atherosclerosis pathogenesis

1. Fatty streak: *endothelial cell damage/dysfunction* → LDL entry into intima where it is *oxidized*→ *monocytes* are recruited from blood and convert to *macrophages* which then *phagocytose* the oxidized LDL forming *foam cells* 2. T-cells follow monocytes into the intima where they release cytokines to intensify inflammation, and the T-cell + foam cells form a *fatty streak*. 3. Plaque progression: smooth muscle cell migration from *media* due to PDGF and produce collagen rich ECM which leads to *fibrous cap* 4. Plaque disruption: hemodynamic stress and degradation of extracellular matrix → fibrous plaque rupture → thrombus formation which can rupture.

Restrictive lung diseases include

1. Idiopathic pulmonary fibrosis 2. Pneumoconioses 3. Sarcoidosis 4. Hypersensitivity Pneumonitis

categoeies of disc herniation pain

1. Inflammatory 2. Biochemical Incsease phospolipase A2, prostaglandins, cytokine and nitric oxide 3. Vascular Increase endoneurial pressure Decrease blood flow in the dorsal root ganglia Compartment syndrome 4. Mechanical compression

Subtypes of Hodgkins

1. Nodular sclerosing: 65-70% of cases 2. Lymphocyte rich: Uncommon form of 'classical' HL 3. Lymphocyte-depleted: Least common form (<5% of cases) 4. Mixed cellularity: 20-25% of cases

glaucoma risk factors

1. Older age or myopia (↑ incidence of open-angle glaucoma) 2. African-American race (↑ incidence of open-angle glaucoma) 3. Asian or Eskimo ancestry (↑ incidence of closed-angle glaucoma) 4. Family history, eye trauma, intraocular inflammation 5. Steroids

prostate zones

1. Peripheral: Contains largest and most numerous glands. The peripheral zone is the area that is palpated on digital rectal exam (DRE) and represents the area where 70% of adenocarcinomas are found. (PSA>4) also susceptible to prostatitis. 2. Central: The central zone is the area surrounding the ejaculatory ducts. This zone consists of 25% of the glandular tissue.Does NOT really give rise to cancer. 3. Transitional (periurethral). This transitional zone is where *benign prostatic hyperplasia* occurs and can lead to bladder outlet obstruction when an adenoma grows to a significant size.

Clinical features of cirrhosis

1. Portal hypertension - Ascites (fluid in peritoneal cavity) - splenomegaly and hypersplenism (consumption of platelets and RBCs from enlarged spleen) - liver failure 2. Decreased detoxification (mental changes, asterixis, b/c NH4)... but is REVERSABLE. Also, excess estrogen and its sides. 3. Decreased protein synthesis (hypoambuminemia leading to edema, coagulopathy due to decrease clotting factors, epoxide reductase) Also Anorexia, Weight loss, Weakness, Hepatocellular carcinoma

3 types of muscle

1. Skeletal muscle: which is striated and voluntary. multi nuclei, striations. 2. Cardiac muscle: which present striations and is involuntary. one nuclei, striations. 3. Smooth muscle: which is non striated and involuntary. one nuclei, no striations.

Five major histologic patterns of tissue reaction in infections

1. Suppurative (Polymorphonuclear) Inflammation 2. Granulomatous Inflammation 3. Necrotizing Inflammation 4. Chronic Inflammation and Scarring (HBV) 5. Cytopathic-Cytoproliferative Inflammation

4 types of basic tissue

1. epithelial 2. connective 3. muscle 4. nerve

bone fracture healing

1. formation of fracture hematoma: bleeding from damaged local vessels collects around fracture site, hematoma forms. Bone cells that are avascular will undergo necrosis, neutrophils and monocytes phagocytose them 2. formation of fibrocartilaginous callus: angiogenesis occurs with capillaries growing into the fracture hematoma. Fibroblasts/osteoblasts proliferate and start the process of repair. The fibroblasts produce collagen fibrls that extend over the break to try and connect the bone ends together. 3. Formation of a bony callus: fibrocartilaginous callus is converted into a bony callus the proliferation of osteoblasts/osteoclasts. 4. Remodeling of bone: osteoclasts remove excess bone, and cancellous bone is replaces with compact bone.

refraction abnormalities

1. myopia, or nearsightedness, which occurs when the eyeball is too long relative to the focusing power of the cornea and lens, or when the lens is thicker than normal, so an image converges in front of the retina. Myopic individuals can see close objects clearly, but not distant objects. 2. In hyperopia or farsightedness, also known as hypermetropia, the eyeball length is short relative to the focusing power of the cornea and lens, or the lens is thinner than normal, so an image converges behind the retina. Hyperopic individuals can see distant objects clearly, but not close ones 3. Another refraction abnormality is astigmatism, in which either the cornea or the lens has an irregular curvature

3 stages of labour

1st stage: Onset to full dilation of cervix 2nd stage: Full dilation to complete expulsion of baby 3rd stage: Delivery of baby to delivery of placenta

Hiatal hernia

2 kinds: 1) *sliding* hiatal hernia occurs when the *gastroesophageal junction AND proximal stomach herniate through the esophageal hiatus*. The diaphragm is *no longer able to contribute to the GEJ pressure* gradient, thereby predisposing the patient to GERD; most hiatal hernias, however, are asymptomatic. 2) A *paraesophageal (rolling)* hiatal hernia occurs when a part of the stomach, usuall the *the gastric fundus* herniates through the esophageal hiatus , *next to (not in) esophagus* Because the GEJ is not affected, this anatomic arrangement does not lead to GERD as much.

tumor supressor genes

2 main genes: 1) p53 2) rb

Primary osteoporosis

2 types: Type 1) Postmenopausal- affects cancellous bone mostly, due to estrogen deficiency increasting clasts and decreasing blasts. Vertebral body compression fracture is most common (leading to kyphosis aka Dowager's hump.... also Colles) Tye 2) Age related/senile. In patients over 75, affects both cancellous and cortical bone. Hip/pelvic/femoral neck fractures. Most likely to damage medial femoral circumflex artery. Serum calcium, phosphate, PTH, alkaline phosphatase are all NORMAL (helps distinguish between osteomalacia)

Cutaneous healing

2 ways: 1) Primary Intention- wound edges brought together, leaves MINIMAL scar formation 2) Secondary intention- Edges are not approximated, granulation tissue fills in the defect. Leaves scar. Myofibroblasts have ability to contract wound and make it smaller (!!!)

Adrenal cortex

3 layers (Glomerulosa- Mineralcorticoids Fasiculata- Cortisol Reticularis- sex steroids

Lymphocytes

3 types: T cells, B cells/plasma cells, NK cells T and B lymphocytes have small amounts of cytoplasm but a round, dense nucleus

Diagnostic mneumonic for SLE

4 out of "SOAP BRAIN MD" -Oral ulcers -Arthritis in 2+ joints (NON-errosive, little deformity) - Photosensitivity (rash via sun) - blood disorders - renal disorders - ANA positive - Neurologic disorders (seizures, psychosis) - Malar butterfly rash, sparing nasal folds - Discoid rash-

Obstructive lung diseases

4 total lung diseases, normal inspiration flow pattern, there is an *obstruction* to getting air *out*.... results in *hyperinflated* lungs 1) Chronic bronchitis 2) asthma 3) emphysema 4) bronchiectasis *chronic brpnchitis + emphysema = COPD+

Lumbar vertebrae

5 The superior and inferior articular processes of the lumbar vertebrae lie in a sagittal plane and thus the lumbar vertebrae can flex and extend but CANNOT rotate. • Due to the large weight bearing load, the lumbar region the most common region for spondylosis and spondylolisthesis. Spondylolisthesis is commonly accompanied with a herniated disc.

BPH

5-AR in prostate converts Testosterone into DHT, which binds to ARs in the prostate. Presentation: • Decreased calibre and force of stream • Trouble starting (hesitancy) and stopping the stream • Postvoid dribbling, urinary retention, incontinence • Urgency, frequency, nocturia, dysuria

Crohns affected regions

50% ileum and colon 30% terminal ileum alone 20% colon alone B/c terminal ileum so involved, can get less bloody diarrhea, and more malabsorption.

5 types of lupus nephritis

6 classes based on a WHO classification Class I (normal) mild Class II (mesangial) mild Class III (focal proliferative glomerulonephritis) moderately severe Class IV (diffuse proliferative glomerulonephritis) severe Class V (membranous glomerulonephritis)- variable (Class VI (glomerulosclerosis) irreversible changes)

prostate cancer

70% arise in the peripheral zone, 15-20% arise in the central zone, and 10-15% arise in the transitional zone. Most (95%) prostate cancers are adenocarcinomas.

spinal nerve numbers

8 cervical 12 thoracic 5 lumbar 5 sacral cervical nerves 1-7 exit above cervical vertebrae 1-7. Cervical vertebrae 8 exits below C7, and above T1. T1 nerve exits below T1 vertebrae.... etc.

large intestine cancer type

98% of all cancers in the large intestine are adenocarcinomas.

Secondary lymphoid organs

: sites of antigenic stimulation of mature naïve lymphocytes → lymphocyte activation. This process is clearly antigen-dependent (i.e., stimulation by foreign antigen is required). • Normally, all secondary lymphoid organs have lymphoid follicles. • Secondary lymphoid organs include: 1. Lymph nodes 2. Spleen 3. MALT (mucosal-associated lymphoid tissue) — e.g., tonsils, adenoid glands, Peyer's patches

Primary lymphoid organs

: sites of lymphocyte birth and/or maturation via a process that does not involve stimulation by foreign antigen (i.e., an antigen-independent process) → mature naïve lymphocytes • Normally, primary lymphoid organs do not contain lymphoid follicles. • Primary lymphoid organs include: 1. Bone marrow 2. Thymus

HAART

= highly active antiretroviral therapy) which usually includes two nucleoside reverse transcriptase inhibitors (NRTIs) with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or one or two protease inhibitors (PIs).

reticulocyte count

A blood test that measures how fast reticulocytes are made by the bone marrow and released into the blood. Increase in R. count in Blood loss or in certain diseases in which red blood cells are destroyed prematurely, such as hemolytic anemia. High altitudes done to See whether anemia is caused by fewer red blood cells being made or by a greater loss of red blood cells. Check to see if treatment for anemia is working.

FAP

AD inherited disorder, characterized by inherited *APC tumor suppressor* mutation, It is the *most common* pathway in colorectal cancer. (*APC-adenoma-carcinoma sequence*) characterized by hundreds to thousands of colonic adenomatous polyps that typically begin to emerge in the second and third decades of life. Colon cancer is inevitable if the colon is not remove, so we remove colon and rectum prophylactic.

central diabetes insipidus

ADH deficiency. Due to hypothalamic or posterior pituitary cause/trauma. Polyuria, Polydipsia - Hypernatremia and high serum osmolality - low urine osmolarity and specific gravity Diagnose with water deprivation test- should result in concentrated urine, but they can't concentrate it. Treat with desmopressin (ADH analog)

Aqueous humor flow

AH is produced in the posterior chamber. (Formed by the pars plicata of the ciliary body). Flows through the pupil into the anterior chamber. Egresses through the trabecular meshwork, into Schlemm's canal.

Acute respiratory distress syndrome (ARDS)

ARDS is an acute lung injury due to an inciting event (trauma, sepsis, acute pancreatitis, amniotic fluid embolism, shock) causing complement activation and subsqeuent *diffuse damage* to *alveolar-capillary interface.* This causes an an increase in alveolar capillary permeability with *leakage of plasma proteins*, RBCS (red blood cells), WBCS (white blood cells), PMNS (polymorphonuclear leukocytes) into alveoli and interstitium This damage causes *formation of an intra-alveolar hyaline membrane* (hallmark of it!!!). Consequences: 1) Increased hyaline membrane formation *impairs gas exchange* (because it is thickened).... and leads to hypoxemia/cyanosis refractory to increased oxygenation 2) Neutrophils cause destruction of *Type I and II pneumocytes* (!!!) → loss of surfactant → *atelectasis*. This causes the formation of an intrapulmonary shunt (A V/Q mismatch with no V)

AML (Acute myelogenous leukemia)

Accumulation of myeloid precursors which are characterized by staining for myeloperoxidase (MPO!!)- Uncontrolled growth of blasts in marrow leads to: • Suppression of normal hematopoietic cells • Appearance of blasts in peripheral blood Clinical Features • Anaemia • Thrombocytopenia (associated with DIC in promyelocytic leukemia) • Neutropenia (even with normal WBC): leads to infections, fever These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection.

Overview and types of Vasodilators

Act by *decreasing TPR* (smooth muscle relaxation of *arterioles*) and/or *decreasing preload* Including - ACE inhibitors - AT-2 receptor blockers (ARBs) - Nitrates - Hydralazine - Calcium channel blockers

Loop diuretics

Act in the *thick ascending limb* on the *NKCC symporter*.(sodium, potassium, 2 chloride by competing for the Cl- binding site. Because magnesium and calcium reabsorption in the thick ascending limb is dependent on the positive lumen voltage gradient set up by *potassium* loop diuretics ALSO inhibit their reabsorption. By disrupting the reabsorption of these ions, they prevent urine from being concentrated in the renal medulla, thus water has less of an osmotic driving force to leave the collecting duct system, ultimately resulting in increased urine. Loop diuretics are used for *high-volume diuresis*, such as in *pulmonary edema* or decreasing fluid overload in *heart failure*. Because of its short duration of activity, it is *not very useful for the treatment of hypertension*. Because of its calcium-wasting effect, it can be used to treat hypercalcemia.

Th cells act have these general functions

Activating and directing other immune cells. They are essential in b cell antibody class switching Activation and growth of cytotoxic T cells Maximizing bactericidal activity of phagocytes such as macrophages.

Fulminant hepatic failure

Acute liver failure with encephalopathy within 8 weeks of hepatic dysfunction: - Acetaminophen OD most common cause, then viral hepatitis

adaptive immunity

Adaptive Immunity: • Involves memory: T and B cell receptors undergo somatic rearrangement (VDJ recombination) which are produced long after infection. • Response to infection is initially slow (often occurring after the innate response). Response is faster upon repeat infection. • Primarily involves T-cells, B-cells and circulating antibodies.

other consequences of renal failure

Additional abnormalities associated with chronic renal failure include: - pruritis - hyperuricemia - ↓ libido secondary to low testosterone levels ↓ erythropoietin production → normochromic, normocytic anemia

treat IBS

Adequate fiber important, eliminate irritant foods (coffee, spices, fatty foods) - antispasmodic-anticholinergic (ie, dicyclomine) - Loperamide for diarrhea (serotonin 3 antagonist) - Lubiprostone for constitipation (Cl- channel activator)

adrenarche

Adrenarche is an early sexual maturation stage in some higher primates that in humans typically occurs at around 6 to 8 years of age. During adrenarche the adrenal cortex secretes increased levels of androgens such as DHEA and DHEAS, but without increased cortisol levels. Adrenarche is the result of the development of a new zone of the adrenal cortex, the zona reticularis The increase in adrenal androgen secretion induces pubarche.

Hyperthyroid diagnosis

After confirming thyrotoxicosis with TSH and free thyroid hormone level assays, 123I uptake may help determine the etiology of the thyrotoxicosis: Graves disease: Diffusely ↑ 123I uptake in the whole thyroid gland. Toxic multinodular goiter: Uneven 123I uptake with occasional autonomous "hot" nodules demonstrating ↑ 123I uptake. Thyroiditis: ↓ 123I uptake Exogenous thyroid hormone intake: ↓ 123I uptake excess thyroid hormone negatively feeds back on the pituitary → ↓ TSH → ↓ thyroid activity (∴ ↓ 123I uptake) with thyroid gland atrophy.

vorpus luteum

After ovulation, the granulosa cells and the cells of the theca interna reorganize to form a temporary endocrine gland called Corpus luteum. production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A- Granulosa cells do not divide - hey increase in size. - They make up most of the corpus luteum (80% of its parenchyma). Cells of the theca undergo transformation - Theca lutein cells.

Trauma guidelines

Airway- (suction, oropharyngeal or nasopharyngeal tube) Breathing (100% or, check resp rate, pule oximetry) Circulation- control bleeding, assess pulse, color, cap refill... use fluids Disability- AVPU (alert, vocal stimuli, painful stimuli, unresponsive) Examine- pupils

Aldosterone receptor antagonists

Aldosterone *normally* adds sodium channels in the *principal cells* of the *collecting duct* and late distal tubule of the nephron.*principal cells* *normally* cause *sodium resorption* AND *potassium exctetion* Spironolactone prevents aldosterone from entering the principal cells. Thus, we have ↓ reuptake of Na → ↓ efflux of K into the urine) (*potassium sparring* Diuresis results as excess Na+ in the lumen of the nephron attracts water, thereby preventing its reabsorption.

Alcohol related liver disease

All forms are damage to hepatic parenchyma 1) Fatty liver- reversible, heavy/greasy/'shiny' liver 2) Alcoholic hepatitis- direct chemical injury due to acetaldehyde. - Swelling/balooning of hepatocytes, necrosis, MALLORY BODIES 3) Cirrhosis AST>ALT

Atopic asthma pathogensis (!!)

Allergens induce TH2 phenotype in CD4+ T cells in *genetically susceptible* individuals TH2 cells secrete: (memorize!!!!) - IL-4 - IL-5 - IL-10 IL-4 allows plasma cell to class switch to IgE IL-5 calls in *eosinophils* (AND B-cells), causes IgA secretion IL-10- inhibits production of Th1, stimulates Th2 to enhance overall reaction.

Emphysema and antiprotease deficiency

Alpha-1-antitrypsin deficiency makes lung more susceptible to protease degeneration.

Consonance

Although the order of pubertal changes is uniform (the smooth ordered progression of changes is termed "consonance") the age of onset and both the pace and duration of changes varies widely from one individual to another female: breast bud, pubic hair, peak height, menarche, pubic hair adult, breasts adult male: genital devt, pubic hair, peak height, genital adult, pubic hair adult

What is a pericyte ?

An Adventitial cell or mural cell - is a connective tissue cell that surround small blood vessels providing support. Relatively undifferentiated cell but it can differentiate into : a fibroblast smooth muscle cell They play an important role in blood-brain barrier stability as well as angiogenesis. They have been implicated in blood flow regulation at the capillary level

aneurysm

An aneurysm is a localized abnormal *dilation of a vessel* due to *weakening of the vessel wall* Aneurysms are classified by *shape and size* and can thus be considered *saccular* or *fusiform* aneurysms. A *saccular aneurysm* is a spherical out-pouching that involves *only a portion* of the blood vessel. This type of aneurysm measures 5 to 20 cm in diameter. A *fusiform aneurysm* involves diffuse and circumferential dilation of a long segment of a vessel and can range in size, but can reach 20 cm in diameter.

heart necrosis

An initial inflammatory response (may last for hours to days). This is followed by a reparative response. (days to weeks). Most infarcts are ultimately replaced by a fibrous scar tissue.(except brain).

causes of ambiguous genitalia

Androgen insensitivity syndrome - pseudohermaphroditism - congenital adrenal hyperplasia

Ischemic heart disease can be grouped into:

Angina pectoris Ischemic cardiomyopathy Myocardial infarction Sudden cardiac death

Angina pectoris

Angina pectoris is pain caused by a *decrease in myocardial perfusion* that normally presents as tightness, squeezing, or heaviness in the chest area. The pain episodes caused by angina pectoris normally lasts *5-10 minutes* unless it has progressed to an ongoing infarction. Angina pectoris is the *most common syndrome of ischemic heart disease* and can present as either: - stable - unstable - prinzmetal angina.

Spondylolisthesis:

Anterior or posterior displacement of the vertebrae in relation to adjacent vertebrae. L4-L5 (often degenerative) and L5-S1 (often congenital) are very commonly involved.

recovered phase

Anti HBV core antibody IgG AND Anti HBs elevated

SLE labs

Anti-neutrophil antibody (ANA) is sensitive (not specific) for screening.... Anti- dsDNA antibody and anti-Sm (Smith) are very specific!! Note: Anti-dsDNA antibody is associated with disease activity, and renal nephritis (!!!) so if titers are high, it predicts poor prognosis. - anticardiolipin antibody, which gives a false positive test for syphilius (on VDRL and RPR tests). These tests look for anti-cardiolipin antibodies. - Another antibody is *lupus-anticoagulant*... this gives falsely-elevated PTT because it interferes with lipids used in PTT test. Note, these patients with lupus anticoagulant can also develop *antiphospholipid antibody syndrome*!!!!

Anti HBe

Antibody to HBeAg... indicates low transmissibility

Anti- HBs

Antibody to HBsAG.... indicated IMMUNITY to hep B. Seen in recovery, immunized

Dendritic Cells

Antigen-sampling and -presenting cells to lymphocytes Express toll-like receptors, pattern recognition receptors, MHC II, and Fc receptor

SLE autoantibodies

Antinuclear antibody (ANA) >96% • Anti-dsDNA 40-60% • Anti-Sm 20-30% (Smith)

Aortic stenosis vs regurge heart sounds

Aortic regurgitation is associated with an S4 heart sound as blood hits the dilated ventricular wall. Note: An S4 can also be heard in aortic stenosis. Differentiate the two by the associated murmur. Aortic stenosis causes a systolic crescendo-decrescendo murmur, which aortic regurgitation causes a diastolic decrescendo murmur.

Epidural Hematoma

Arterialized bleeding results in rapid expansion of hematoma and neurological decline. Often presents with brief loss consciousness, followed by lucid interval of minutes to hours, before rapid neurological decline into coma. Biconvex, *lenticular* shape. generally the result of trauma in the *temporal bone* that causes a tear in the middle meningeal artery. Herniation typically causing contralateral hemiparesis and ipsilateral pupillary dilation

Artery layers

Arteries consist of: - a tunica intima - tunica media - tunica externa/adventitia.

arterioles

Arterioles are the resistance vessels. Though individual capillaries actually have the highest resistance, their *parallel* arrangement reduces their contribution to total peripheral resistance below that of the arterioles.

sickle cell formation

At low O2 tension, HbS polymerizes (the substituted Val residue allows for hydrophobic interactions to occur between Hb chains) → RBCs sickle and de-sickle, causing RBC cell membranes to stiffen and damage, becoming more likely to hemolyze.

Huntington's brain

Atrophy of the caudate with resultant increase in size of lateral ventricles. The globus pallidus may be atrophied secondarily, and the lateral and third ventricles are dilated. Atrophy is frequently also seen in the frontal lobe, less often in the parietal lobe, and occasionally in the entire cortex.

prevent SLE

Avoid sun, use sunscreen - avoid estrogen COCP - healthy diet

Consequences of chronic renal from azotemia

Azotemia: ↑ BUN and ↑ serum Cr Symptoms BASED on azotemia: - nausea, vomiting - neurologic dysfunction: mental status changes, encephalopathy, asterixis, coma - hemorrhagic fibrinous pericarditis ↑ risk of infection due to uremia-induced dysfunction of neutrophils and other white blood cells ↑ risk of bleeding due to uremia-induced platelet dysfunction (↑ bleeding time; normal PT, PTT) Uremia is a syndrome of severe renal failure with azotemia (↑ BUN and serum Cr) + manifestations described above (e.g., acidosis, hypertension, fluid overload, anemia, hyperkalemia, hypocalcemia, bleeding diathesis, etc).

Summary, NHL B-cell lymphomas

B-cell Lymphoma: originate from B-cells within the germinal follicle and include: -Burkitt's Lymphoma -Diffuse large B-cell lymphoma (DLBCL) -Follicular lymphoma -Small lymphocytic lymphoma (SLL) -MALToma

BCL2 and follicular lymphoma

BCL2 stabilizes mitochodrial membrane by prohibiting cytochrome C from leaking from mitrochondria into cytoplasm. This BLOCKS apoptosis, which is what you usually want. Note: you actually WANT apoptosis in follicle more than almost any other place, because in follicle we get somatic hypermutation of B cells where they are challenged with 'selection', and vast majority fail (undergo apoptosis), some pass. This translocation allows cells that should have died, to survive.

Barrett's is risk factor for what ?

Barrett's is THE major risk factor for esophageal* adenocarcinoma* (most often occurs in the distal 1/3 of the esophagus) Adenoma is malignant prolifferation of glands... glands are NOT normally in esophagus, except from *Barrett's metaplasia*... which progresses to *adenocarcinoma* This is most common type of esophageal cancer in the West.

Type 4 collagen

Basement membrane. Glomerulonephritis of Alport syndrome; the dysfunctional basement membranes in the kidneys leads to ESRD (end stage renal disease)

Protein digestion

Begins in stomach with pepsin, converts some proteins to peptides Enzymes in pancreatic juice—trypsin, chymotrypsin, carboxypeptidase, and elastase—continue to break down proteins into peptides.Their actions differ somewhat because each splits peptide bonds between different amino acids.

benign vs malignant neoplasms

Benign Usually well differentiated Usually slow growing Forms cohesive, expansile, well-demarcated masses No metastasis Malignant Range of appearances Erratic, slow to rapid Infiltrates and destroys surrounding normal tissues Potential for metastasis

Adenomatous aka neoplastic polyp

Benign neoplastic prolifferation of glands, but is *premalignant*, and can progress to *adenocarcinoma* via the *adenoma-carcinoma sequence* Ranked in order of increasing malignant dysplasia potential:( least malignant to most malignant) 1) tubular adenoma 2) tubulovillous adenoma 3) villous adenoma *potential neoplastic* polypys are usually: - greater than 2cm size - grows in *sessile pattern* - has long *villous* like projections ("villous is the 'villian")

Bilirubin metabolism 2

Bile released into duodenum, 95% is reabsorbed by terminal ileum and reaches liver by portal circulation and is re-secreted by liver into small intestine (called enterohepatic circulation) 5% of originally secreted unconjugated bilirubin is metabolized by colonic bacteria to form urobilinogen. Urobilinogen oxidized into urobilin (makes urine yellow) and stercobilin (makes stools brown).

Anticholinergics in asthma

Blocks acetylcholine-induced bronchoconstriction (ACh ↑ bronchial smooth muscle tone) Best used for maintenance and is more effective for COPD patients (not important)

Regulatory T-cells

CD4+ T-cells that suppress immune responses. Act via: 1) can block T-cell activation. Regulatory T-cell expresses *CTLA4* which competes with B7... this decreases chances of CD28 and B7 binding for the *second signal*, and therefore the T-cells undergo anergy. 2) Secrete cytokines: - IL-10- inhibits macrophages and dendritic cells, limits expression of MHC II, so there is less binding to TCR... it also limits production of B7 and other *costimulatory* molecules - TGF-B also inhibits activation of macrophages

CF

CFTR Gene defect: Cl- channel defect --> thick viscous mucus obstructing ducts of exocrine organs and eccrine sweat glands. • Multisystem disease affecting digestive system, sweat glands, and reproductive tract - but progressive lung disease continues to be main cause of mortality. • The usual presenting symptoms and signs include persistent pulmonary infection, pancreatic insufficiency, and elevated sweat chloride levels. However, many patients demonstrate mild or atypical symptoms. - nasal polyps and chronic rhinitis - persistent, productive cough - pancreatic insufficiency (malabsorption), Vitamin ADEK deficiency, failure to thrive

Myelin CNS vs PNS

CNS: one oligodendrocyte myelinates multiple internodes on multiple axons Therefore, the death of just a few oligo's can have a big impact PNS: one Schwann cell myelinates only one internode on a single axon

birth control options

COCP- prevent ovulation Pogesterone only pill, or implant- thicken cervical mucus, sometimes prevents ovulation

Hypothroidism Cardiovascular

Cardiovascular: - Peripheral vasoconstriction to maintain body heat → cool, pale, dry skin - ↓ Synthesis of cardiac β1 receptors → - ↓ HR (bradycardia) - ↓ contractility → ↓ SV (stroke volume) ∴ ↓ PP (pulse pressure) - ↓ HR and ↓ SV → ↓ CO (cardiac output) → ↓ exercise capacity, shortness of breath

Cataract risk factors

Cataract (leading cause of blindness): painless, bilateral opacification of the lens of the eye leading to decrease in vision 1. ↑ Age 2. Cigarette smoking 3. Prolonged UV radiation exposure 4. Trauma 5. Uncontrolled diabetes mellitus (sorbitol) 6. certain drugs (corticosteroids)

mantoux test categories

Category 1- 5-9mm individuals who have had contact with actively infected TB patients and HIV-positive patients Category 2 - 10-14mm includes HIV(-) intravenous drug users, high-prevalence countries, persons with medical conditions that put them at risk for progressing from latent TB to active TB, Category 3- 15+ mm includes individuals who do not meet criteria in the other categories.

SLE pathogenesis

Cells undergo apoptosis (ie, from DNA damage), and release nuclear debris. Self reactive B-lymphocyte may be exposed, and it produces anti-nuclear antigens. The next time there is more apoptosis, you have antigen-antibody complexes at low levels, which are taken up by dendritic cells, and they activate *toll like receptors* in dendritic cells which amplify immune response, amplify production of high levels of *antigen-antibody complexes*.

Hypothyroidism CNS

Central Nervous System: - Slow DTRs with prolonged relaxation phase - Fatigue - Lethargy - Mental slowness - Mental retardation (perinatal)

concussion

Change in the momentum of the head Transient mental status alteration (eg, loss of consciousness or memory) lasting < 6 h

TPR and cardiac cycle

Changes in TPR affect both the cardiac output (CO) and the venous return, such that *increased TPR* causes *decreased venous return* (blood retained on arterial side behind constricted arterioles) AND *decreased CO* (by increased afterload), and *decreased TPR* causes *increased venous return* (with more blood reaching the venous side) AND *increased CO* (by the Frank-Starling mechanism (increased preload), as well as decreased afterload). In both cases, a new equilibrium point (intersection of venous return and CO) is established, but *right atrial pressure is unchanged.*

infective endocarditis

Characterized by invasion of the heart valves or the mural endocardium by a microrganism Formation of bulky, friable vegetations (thrombotic debris and organisms) associated with destruction of the underlying cardiac tissue The aortic and mitral valves are the most common sites of infection

Bronchopneumonia

Characterized by scattered patches of isolated acute consolidation, centered around bronchioles, that affects more than one pulmonary lobe (often bilateral too).

HBV acute to chronic by age

Chronic infection develops in about 90 percent of children who are infected at birth (associated with failure to produce antibody to HbsAg) in 20 to 50 percent of children who are infected between the ages of 1 and 5 years and in less than 5 percent of people infected with hepatitis B during adulthood

Renal disorders in SLE

Class IV lupus nephritis: diffuse proliferative glomerulonephritis (nephritic syndrome) — most common and most severe form of lupus nephritis; most common cause of death (!!!!) characterized by hypertension and hematuria. commonly has "wire-loop" lesions due to prominent subendothelial immune-complex deposits -membranous glomerulonephritis- proetinuria (nephrotic syndrome)... Can get combination of both nephritic and nephrotic.

Non Hodgkin Lymphoma

Classify it by: - Cell type (B cell vs T-cell) - Cell size (small vs intermediate vs large) - pattern of cell growth - expression of surface markers - cytogenic translocations When lymphocytes are neoplastic they can be small, medium or large. When small neoplastic, they are usually well differentiated (look very similar to normal lymphocytes, so they grow in similar patterns). So we can have: - Follicular lymphoma - Mantle cell lymphoma - Marginal zone lymphoma

clinical features compartment syndrome

Clinical Features • Persistent deep ache or burning pain • Paresthesias (suggests ischaemic nerve dysfunction) • Pain with passive stretch of muscles in affected compartment • Tense compartment with firm "wood like" feeling • Pallor from vascular insufficiency • Diminished sensation • Muscle weakness

clinical uses of K+ sparing diuretics

Clinical uses: *Amiloride* is used in the treatment of heart failure when *hypokalemia is a concern*, such as concomitant loop diuretic use. *Spironolactone* is also used in severe heart failure as well as in *aldosterone-secreting tumors* before surgical correction.

ACE inhibitor uses

Clinical uses: ACE inhibitors are typically used in: - *hypertension* due to the vasodilation effect - * heart failure* because AT II causes maladaptive remodeling in the failed heart, thus ACE inhibition slows the progression of heart failure; - in diabetes because AT II preferentially vasoconstricts the *efferent arteriole* (the arteriole leaving the glomerulus), and *blocking* that *vasoconstriction* decreases glomerular pressure, slowing the progression of kidney damage in diabetes.

CR cancer diagnosis

Clinically, colonoscopy + biopsy is the gold standard for diagnosis of colorectal adenocarcinomas. Carcinogenic embryonic antigen (CEA) can be used to monitor disease progression and recurrence, but is a poor screening test.

A2 agonists

Clonidine/methyldopa The α2 receptor acts as negative feedback for the sympathetic nervous system. Using an α2-receptor agonist causes a *net decrease* in *sympathetic outflow* in the vasomotor center of the medulla to decrease presynapstic norepinephrine release.

Thyroid colloid

Colloid: central space in follicle where thyroid hormone is stored as a component of thyroglobulin Papillary thyroid cancer: common in women, particularly in their 20s or 30s, and in patients with prior neck radiation Thyroglobulin is a marker for well differentiated papillary thyroid cancer Look for characteristic Orphan Annie eye nuclear inclusions (nuclei with uniform staining, which appear empty), and psammoma bodies (round concentric collection of calcium) on light microscopy.

Colorectal cancer

Colorectal cancer is the second leading cause of cancer-related deaths in the U.S. Adenocarcinoma is the most common malignancy of the large intestine. 2 forms: -Familial adenomatous polyposis (FAP) - Hereditary non-polyposis colorectal cancer (HNPCC)

macula densa

Columnar epithelium thickening of the distal tubule that adheres to the vascular pole of glomerulus They are sensitive to the ionic content and water volume of the fluid in the tubule (osmoreceptors). Macula densa senses when there is low sodium in the distal tubule or afferent arteriole, acts as osmoreceptor to increase release of renis

treat TB

Combination drug therapy is used to delay/prevent resistance and to provide additive effects against TB. • Primary drugs are: RIPE • Isoniazid (INH) • Rifampin • Ethambutol • Pyrazinamide

common causes of pre-renal azotemia induced ischemia ATN

Common causes of pre-renal azotemia that can progress to ischemic ATN include hypovolemia, impaired cardiac function, hypoalbuminemia, renal artery stenosis, and NSAID use. Hypovolemia induced ATN is seen in shock, vomiting, hemorrhage, dehydration, diuretic use. Decreased cardiac output can be caused by many pathologies such as congestive heart failure, aortic stenosis and aortic regurgitation. NSAIDs cause decreased blood flow because they inhibit prostaglandin synthesis. Prostaglandins *normally dilate the afferent arteriole, which increases renal blood flow*. If this is blocked, the afferent arteriole doesn't dilate and there is not enough renal blood flow.

Multiple myeloma symptoms

Common features can be remembered with mnemonic: "MM patients can be crabby" → "CRABBI" HyperCalcemia Renal insufficiency Anemia Bence-Jones proteinuria Bone lesions (lytic) Infections

Thiazolidinediones

Commonly used medications include rosiglitazone, and pioglitazone. Mechanism: Improves insulin target sensitivity. It binds to PPAR-γ (peroxisome proliferator activating receptor-gamma), causing increased insulin receptor number and sensitivity, as well as decreased hepatic gluconeogenesis. Side effects include hepatotoxicity and cardiovascular toxicity. Absolute contraindication in pts with liver failure or CHF.

Hydatidiform Mole

Complete moles are characterized by extensive proliferation of trophoblastic tissue, hydropic villi and absence of foetal vessels. Complete hydatidiform moles typically have a 46 XX karyotype but with both X chromosomes derived from the father. In an incomplete mole, hyperplasia of trophoblastic tissue is less marked, some villi are essentially normal and foetal vessels are present. Incomplete (Partial) moles usually have a triploid karyotype 80% of which are 69 XXY. The remainder are 69 XXX or 69 XYY. An invasive hydatidiform moles is locally destructive and may invade parametrial tissue and blood vessels. Hydropic villi may embolize to distant sites, such as lungs and brain, but do not grow in these organs as true metastases

Cachexia

Complex metabolic syndrome associated with underlying illness —loss of muscle with or without loss of fat mass causes: Systemic inflammation mediated through cell injury of activation of the immune system triggers an acute inflammatory response that causes excess cytokine release. TNF-a and IFN-Y cause proteolysis of myosin heavy chains Increased cortisol increased catecholamine release

Complications of aortic stenosis

Concentric *LV hypertrophy* as it pumps against the stenotic aorta Triad of SAD symptoms: - Syncope (↓ blood flow to brain) - Angina (↓ blood flow through coronary arteries in diastole), -Dyspnea *symptoms initially present during exercise, later at rest* Microangiopathic hemolytic anemia (some of the blood cells rupture as they flow past calcified aortic valve).

Osteogenesis imperfecta

Congenital defect of bone formation resulting in WEAK bone, most often due to AD defect in type 1 collegen (mnemonic, bONE has 'one' in it) - multiple fractures- - blue sclera (normally has type 1 collagen, but this is defective, so choroidal veins are exposed making eye blue) - hearing loss (fractures ossicles)

kidney mesangial cell

Contractile Part of juxtaglomerular apparatus Have receptors for angiotensin II and natriuretic factor produced by cardiac atria cells (vasodilator, increasing blood flow and increasing the surface area for filtration) Structural support Synthetise extracellular matrix, endocytose and dispose of molecules (immune complex) Generation of prostaglandins (PGs) and mediators of inflammation

Stable angina tests

Coronary arteries begin in epicardium, and extend down to feel all layers (myocardium and endocardium)... the area underneath the endocardium is most succeptible to ischemic damage, so it give *subendocardial* ischemia. The HALLMARK of *sub-endocardial* ischemia is *ST depression* During stable angina pectoris episodes there is *no elevation in troponin* levels

killer t cell signalling

Cytotoxic (CD8+) T cell activation: • First signal: *intracellular* Antigen presentation via MHC-I of a virus-infected cell.* This is recognized by TCR on the cytotoxic T cell. The CD8 co-receptor stabilizes this interaction. • Second signal: IL-2 secreted by Th1 cells binds IL-2R on CD8+ cells → activation to kill the virus infected cell. CD8+ t-cell secretes: -perforin which creates pores in membrane of target cells - granzymes, which then enter the pore and activates caspases to induce *apoptosis*

CNS vs PNS nerve healing

Damage to the CNS results in the formation of gliosis, this is a permanent scarring of the nervous system. In the peripheral nervous system axons may slowly regrow

Red hepatization

Develop an *exudate* in lung containing neutrophils and *blood*, which gives the normally spongy lung a solid consistency.

Hemorrhoids

Develop due elevated venous pressure within the hemorrhoidal plexus. Predisposing influences Straining at stool - constipation The venous stasis of pregnancy. May also develop as a result of portal hypertension, where the implications are more ominous.

test for h-pylori

Diagnosis is made with endoscopy and biopsy with urease testing, which tests for the production of ammonia by urease-producing H. pylori, leading to an increase in pH of the agar well. A test to monitor treatment response is the urea breath test, which is positive for urease-producing H. pylori when labeled carbon dioxide is exhaled. This may also be used as a secondary diagnostic method. Histology of gastric or duodenal biopsy can demonstrate gastritis, ulcers, or metaplasia. Individuals taking proton-pump inhibitors (PPIs) may have a false negative urease test.

Diastolic murmurs

Diastolic murmurs: 1) Aortic/Pulmonic Regurgitation 2) Mitral/Tricuspid Stenosis Think "sten-O-sis": problem with valve Opening → murmurs secondary to stenosis occur when the involved valve is opening (i.e. mitral/tricuspid value opens in diastole, thus mitral/tricuspid stenosis is a diastolic murmur)

Pulse pressure:

Difference between systolic and diastolic pressure; depends mainly on SV. Decreased vessel capacitance secondary to aging (think stiffer pipes) increases the pulse pressure since systolic pressure increases as diastolic pressure decreases. Pulse pressure = systolic pressure - diastolic pressure MAP = diastolic pressure + 1/ 3 × (pulse pressure)

Granulomatous Inflammation

Diffuse, predominantly mononuclear, interstitial infiltrates. Often seen acutely as a response to viruses, intracellular bacteria, or intracellular parasites. Caused by infectious agents that resist eradication (e.g., M. tuberculosis, Histoplasma capsulatum, schistosome eggs) and are capable of stimulating strong T cell-mediated immunity, so the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Granulomatous inflammation is characterized by "Epithelioid" cells (activated macrophages), which may fuse to form giant cells called *Langhans cells*, with inner pink *caseous necrosis* and surrounded by T-cells. • Assmann focus = apical lung lesion that begins as small caseating tuberculous granuloma - characteristic of secondary infection. Kept small in those with strong immune systems. If the immune system is weak, the apical lesion grows and destoys lung, with increased risk of erosion into blood vessels or airways. Type IV delayed hypersensitivity reaction

candidiasis

Diploid yeast. Cultures show hyphae, pseudohyphae, or budding yeast cells. Esophagitis — presents as retrosternal pain upon swallowing. Note: Candida esophagitis is considered an "AIDS-defining" illness

IBS

Disease of the entire gastrointestinal tract in which a person reacts to stress by developing symptoms (such as cramping and abdominal pain) associated with alternating patterns of diarrhea and constipation. Excessive amounts of mucus may appear in feces; other symptoms include flatulence,nausea, and loss of appetite. most common functional bowel disorder more common in females -abdominal pain revealed by defecation - feeling of incomplete defecation (tenesmus)

Diagnose back pain

Divide into back dominant, or leg dominant Back dominant and constant: inflammatory/mechanical Back dominant and intermittent: likely to be disc herniation (central) or facet joint Leg dominant and constant: disc herniation (lateral) Leg dominant and intermittent- spinal stenosis

Elastic fibers lost in emphysema

Due to imbalance of *proteases* compared to *anti-proteases* (main anti-protease is *alpha 1 anti-trypsin*. When we breathe in, it is filtered (mostly by mucus) to keep *distal lung* clean from debris. Bottom of lung has no defence mechanisms except *alveolar macrophage*. When macrophages eat them, there is some inflammation, and this inflammation produces *proteases* as a *by produce of inflammation*. Normally proteases to antiproteases are in balance, but in emphysema we have imbalance in the ratio. SMOKING increases proteases (big time)... while a-1-antitrypsin deficiency impairs antiproteases.

Unstable angina tests

During an unstable angina pectoris episode, the EKG may or may not show ST depression but there will be no ST elevation.

Bronchiectasis presentation

Dyspnea, presence of a *productive cough*. It is more of a chronic cough with purulent- foul smelling sputum. Complications include hypoxemia with cor pulmonale...

Prinzmetal angina tests

EKG shows *ST-elevation* due to *transmural ischemia*... Coronary artery starts in the epicardium, and the spasm cuts off blood supply to the entire wall.... and the classic finding for *transmural ischemia* is *ST elevation*

causes of early menopause

Early menopause can be induced by: smoking, alcohol, radiation, chemotherapy and hysterectomy

Emphysema

Emphysema is am *obstructive* lung condition highlighted by pathological enlargement of distal airways due to destruction of *alveolar walls and alveolar sacs* with *increased elastase* activity *Elastic recoil fibers* are *lost*, so lung compliance *increases* which result in *enlarged airspaces* and barrel chest. Pathoma: Normally think of lung as bunch of balloons, while in emphysema, think of air sacs as a *shopping bag*. Air shoots out of a balloon, not a shopping bag. Elastic tissue is destroyed → loss of radial traction → *collapse of small airways* when exhaling!!!! (due to loss of elastic tissue) → *air trapping*

Cirrhosis

End stage liver damage, characterized by disruption of hepatic parenchyma by: - bands of fibrosis (mediated by TGF-B from STELLATE cells beneath endothelial cells which line sinusoids, in the *perisinusoidal space*) - regenerative nodules of hepatocytes (with fibrosis bands separating nodules) - vascular architecture disrupted

Iodine deficiency

Endemic dietary iodine deficiency is the most common cause of hypothyroidism worldwide

Endometrial Hyperplasia

Endometrial hyperplasia usually results with conditions of prolonged oestrogen excess and can lead to metrorrhagia (uterine bleeding at irregular intervals), menorrhagia (excessive bleeding with menstrual periods), or menometrorrhagia. Endometrial hyperplasia is an important condition as it may denote a premalignant state and also because of its relationship with endometrial carcinoma. Involves the proliferation of endometrial glands that results in a greater than normal gland-to -stroma ratio.

Endothelial damage

Endothelium has protective functions against thrombosis. 1. Produces prostacyclin (PGI2) and NO 2. Secretes heparin like molecules- 3. Secrete tPA 4. Secretes thrombomodulin

epidural vs subdural layer hematoma

Epidural hematoma, leads to accumulation of arterial blood between the dura and the skull. In a subdural hematoma , damage to bridging veins between the brain and the superior sagittal sinus leads to the accumulation of blood between the dura and the arachnoid.

Ependymal Cells

Epithelial cells that line the CSF-filled ventricles in the brain and form the specialized choroid plexus epithelium which secretes the cerebrospinal fluid (CSF). Their apical surfaces are covered in a layer of cilia, which circulate CSF around the central nervous system The lack of tight junctions between ependymal cells allows a free exchange between cerebrospinal fluid and nervous tissue.

Microcytic anemia

Erythroblast keeps dividing, and with each division, cells become smaller, so microcytosis is due to an "extra" division. - Always due to decreased production of Hb. If there isn't enough Hb, RBC's divide an extra time to try and maintain concentration of Hb. 1) iron deficiency anemia 2) Anemia of chronic disease 3) sideroblastic anemia 4) thalassemia

DKA

Excessive serum ketoacidosis (β-hydroxybutyrate and acetoacetate), often with stress/infection (epi ↑ glucagon and thus ↑ lipolysis, glycogenolysis, glucogenesis). - Hyperglycemia (>300 mg/dl) - Metabolic acidosis - Hyperkalemia (due to less insulin, and also due to acidosis buffering bringing H+ into cell and K+ out of cell.... however, a lot of K+ is lost in the urine, so intracellular and total body K+ is low) - Kussmaul respirations (rapid and deep breathing), -fruity" odor on breath -abdominal pain

Extramedullary hematopoiesis results in:

Extramedullary hematopoiesis in the liver and spleen results in hepatosplenomegaly. Hypersplenism, from extramedullary hematopoiesis and increased extravascular hemolysis, can result in splenic infarction and abdominal pain. Note, the increased hemolysis can also lead to bilirubin gallstones leading to RUQ pain. Extramedullary hematopoiesis in the skull results in crewcut appearance on x-ray (!!!). Extramedullary hematopoiesis in the facial bones results in characteristic chipmunk facies (!!!!). Extramedullary hematopoiesis results in increased erythroid precursors leading to an increased risk of aplastic crisis from parvovirus B19 infection (!!!!) - this virus affects erythroid precursors and shuts them down. Normally, it only lasts a week or two, and has little effect because people normally have more than enough RBC reserve. However, these people don't have enough reserve for even a day or so.

Chronic Inflammation and Scarring

Exuberant scarring leading to organ dysfunctionie, Hepatitis. The effectiveness of the cytotoxic T-lymphocyte (CTL) response is a major determinant of whether a person clears the virus or becomes a chronic carrier. When infected hepatocytes are destroyed by CTLs, replicating virus is also eliminated and the infection is cleared. But if the rate of infection of hepatocytes outpaces the ability of CTLs to eliminate infected cells, a chronic infection is established. This may happen in about 5% of adults and up to 90% of children infected perinatally.

manage compartment syndrome

Fasciotomy to fully decompress all involved compartments Splint/cast it.

Leukoencephalopathy (PML)

Fatal viral disease that is characterized by progressive multifocal degeneration of white matter of the brain The cause of PML is a type of polyomavirus (papovavirus) called the JC virus (JCV - John Cunningham virus)

Non-alcoholic fatty liver disease

Fatty change, hepatitis and/or cirrhosis WITHOUT alcohol or other insult. Often due to obesity. ALT>AST

Firecracker malaria life

Female Anopheles mosquito bite → haploid sporozoites in mosquito saliva enter bloodstream. sporozoites infect hepatocytes → sporozoites divide asexually and produce merozoites, bursting the hepatocyte. In P. vivax and P. ovale some of the sporozoites do not immediately undergo asexual replication, but enter a dormant phase known as the hypnozoite. merozoites infect RBCs and divide asexually into characteristic trophozoites. During the trophic period the parasite ingests the host cell cytoplasm and breaks down the hemoglobin into amino acids. trophozoites mature into schizonts, which rupture the RBC to release merozoites merozoites which then spread to infect other RBCs As an alternative to schizogony some of the parasites will undergo a sexual cycle and terminally differentiate into either micro- or macrogametocytes.

uterine prolapse degrees

First degree: The cervix droops into the vagina. Second degree: The cervix sticks to the opening of the vagina. Third degree: The cervix is outside the vagina. Fourth degree: The entire uterus is outside the vagina. This condition is also called procidentia. This is caused by weakness in all of the supporting muscles.

BCl-2 overactivation in

Folicular lymphoma. A translocation between chromosome 14 and 18 results in the overexpression of the bcl-2 gene. As the bcl-2 protein is normally involved in preventing apoptosis, cells with an overexpression of this protein are basically immortal. The bcl-2 gene is normally found on chromosome 18, and the translocation moves the gene near to the site of the immunoglobulin heavy chain enhancer element on chromosome 14.

Toxoid vaccines

For bacteria that secrete toxins, or harmful chemicals, a toxoid vaccine might be the answer. These vaccines are used when a bacterial toxin is the main cause of illness. Scientists have found that they can inactivate toxins by treating them with formalin, a solution of formaldehyde and sterilized water. Such "detoxified" toxins, called toxoids, are safe for use in vaccines. When the immune system receives a vaccine containing a harmless toxoid, it learns how to fight off the natural toxin. The immune system produces antibodies that lock onto and block the toxin. Vaccines against diphtheria and tetanus are examples of toxoid vaccines.

ectopic pregnancy 4 outcomes

Four outcomes: 1. Intratubal hemorrage → Hydrosalpinx 2. Tubal rupture 3. Spontaneous regression w/ absortion of the products of conception 4. Extrusion into abdominal cavity.

Colles fracture

Fracture of distal radius (and distal fragment displaced posteriorly)

cervical fractures

Fractures at the cranial junction, atlas or axis are the most fatal while fractures at the CV6 or CV7 level are the most common due to cervical lordosis

Complications of HBV

Fulminant hepatitis: submassive to massive hepatic necrosis with acute liver failure (7% of cases) Hepatocellular carcinoma secondary to postnecrotic cirrhosis (because of inactivation of p53 and activation of proto-oncogenes. ) (20% of cases)

Ito's cells in space of Disse

Function : Storage and release of retinoids (Vit A) Synthesis of extracellular matrix proteins and proteoglycans Secretion of growth factors and cytokines Sinusoidal lumen regulator

hunger hormones

GI hormones and hunger • Decrease appetite: - Leptin (chief cells and adipose) - Peptide YY (L cells in ileum/colon) - CCK (I cells in duodenum/jejunum) • Increase appetite: - Ghrelin (gastric mucosa)

Myenteric plexus

GI tract has 1) Mucosa 2) submucosa 3) muscularis 4) serosa Muscularis propria has inner circular layer, and outer longitudinal layer.

Necrotizing Inflammation

Gangrene Large necrotic ulcer with overlying exudate and surrounding erythema, edema. The primary cause of gangrene is reduced blood supply to the affected tissues, which results in cell death. Diabetes and long-term smoking increase the risk of suffering from gangrene.

Gastric carcinoma spread

Gastric cancer spreads early and aggressively, then invades into the gastric wall. Gastric cancer commonly metastasizes to nodes/liver and other sites including: Left supraclavicular lymph node: *Virchow node* (The left supraclavicular lymph node drains the stomach). Distant metastasis involves: - Liver

Ischemic heart disease

Group of syndromes related to myocardial ischemia, causes by *compromised blood flow* in coronary vessels, usually due to atherosclerosis of cornonary arteries. Ischemic heart disease can be caused by: - Decreased coronary *blood inflow* (arterial perfusion) - Decreased coronary *blood outflow* (venous drainage) Myocardial ischemia occurs when the myocardial demand for oxygen is greater than the supply. Hypoxic injury occurs, due to decreased delivery of O2 and nutrients into myocardium. The heart compensates for this by ventricular dilation.... ultimately congestive heart failure.

H zone

H-band - zone of myosin filaments only (no overlap with actin filaments) within the A-band During muscular contraction, the region of the H zone will shrink

Two types of HDV infection

HDV requires HBsAG for assembly. 1. simultaneous (co) delta and hepatitis B infection. Simultaneous infection with both delta and hepatitis B may result in clinical hepatitis that is indistinguishable from acute hepatitis A or B, but it may manifest as a second rise in liver enzymes (AST, ALT). 2. Persons with chronic hepatitis B who acquire superimposed infection with hepatitis D suffer relapses of jaundice and have a high likelihood of developing chronic cirrhosis. Superimposed infection is worse. In co-infection, the patient has both anti-HBc and anti-D antibodies, whereas in superinfection, the anti-HBc is absent.

HIV infection stages

HIV gets into cell by attachment: • Using: gp120, gp41 • Attaching to: Cd4 • Using: Co-receptors - Early on in the infection = CCR5 --> Shifts later to CXCR4 • --> Attach 2. Dump the virion into the host cell --> Uncoding to replicate virus 3. Release of RNA • Reverse transcriptase takes ss(+)RNA and convert it to dsDNA 4. Integrase: Integrate that viral DNA into the genome 5. Every time you get transcription from that area of the genome, you are going to make virus. 6. mRNAs you make will be: • Uncleaved --> used as viral genome • Cleaved --> used for protein synthesis (structural and unstructural = integrase, reverse transcriptase, etc) 7. Viral assembly 8. Leave host cell, taking with it the cell membrane as itʼs envelope.

O2 dependent killing

HOCl generated by oxidative burst in phagolysosomes. O2--> O2- (by NADPH oxidase, this is oxidative burst) O2- --> H2O2 (SOD) H2O2 --> HOCl (by myloperoxidase, into bleach)

HSV-2

HSV-2 usually causes infection *below the waist (e.g, herpes genitalis)* however, possibly due to oral sex practices, HSV-2 infection above the waist (e.g., herpes labialis) is sometimes observed. After primary infection, HSV-2 remains latent in *sacral nerve ganglia)*, but may reactivate in response to some stressor.

Hashimoto thyroiditis pathogenesis

Hashimoto thyroiditis is caused by autoimmune failure of self-tolerance to thyroid auto-antigens → thyroid cell death due to: 1) CD8+ T-cell mediated cell death 2) Cytokines activate TH1 → IFN-γ recruits and activates macrophages → follicle damage 3) Anti-thyroid antibodies: - Anti-Tg (thyroglobulin) antibodies - Anti-TPO (thyroid peroxidase) antibodies — ... note do not mediate the diease, they are markers the thyroid has been damaged. Associated with HLA-DR3 and HLA-DR5 (impt!)

Heart murmurs

Heart murmurs can be recognized by: 1. Identifying which auscultation area produces the loudest murmur 2. Identifying whether it is systolic or diastolic 3. Identifying whether it is left or right sided (↑ intensity on inspiration if *right sided*)

helper T cell signalling

Helper (CD4+) T cell activation: Initial step: EXTACELLULAR antigen is phagocytosed, processed, presented by APC (ie macrophage, dentritic cell). This is followed by two co-stimulatory signals. • First signal: Antigen presentation via MHC-II is recognized by the TCR (T-cell receptor) of the T helper cell. • Second signal: Interaction of B7 on the APC with CD28 on the T helper cell. (nemonic, 28/7=4) • In the absence of the second signal, a state of anergy occurs where the cell becomes unresponsive to that particular epitope.(*peipheral tolerance*!!!) Activated CD4+ T-Cells then act via: TH1- secrete: (to help CD8+ cells!!!) 1) IL-2 (which is a T-cell growth factor, and CD8+ T-Cell activator) 2) IFN-y (macrophage activator) TH2 secrete: (to help B cells!!!) 1) IL-4 (class switching to IgG and IgE) 2) IL5 (eosinophil chemotaxis and activation, maturation of B-Cells to plasma cells, and class switching to IgA) 3) IL-10- (Inhibits Th1 phenotype) 4) IL-13 (similar to IL-4)

Nephritic syndrome vs. nephrotic syndrome

Hematuria (4+ blood on urine dipstick) is a prominent feature of nephritic syndrome, with dysmorphic RBCs & RBC casts on urinalysis—vs. nephrotic syndrome: urinalysis reveals fatty casts (oval fat bodies) which demonstrate "maltese cross" interference pattern under polarized light due to cholesterol Hallmark of nephritic syndrome: RBC casts Proteinuria may be present in nephritic syndrome but is usually mild (<3.5g/day)—vs. nephrotic syndrome: >3.5g/day (4+ protein on urine dipstick) Edema may be present in nephritic syndrome but is usually mild (eg, periorbital edema) and is due to salt retention—vs. nephrotic syndrome: generalized edema (anasarca) due to hypoalbuminemia *Nephritic syndrome* is characterized by *neutrophil-mediated glomerular injury*—vs. *nephrotic syndrome* mediated by *T-cells and cytokines damage podocytes and cause podocytes to lose their negative charge*, in turn causing them to fuse and decreasing their effectiveness as a filtration barrier to negatively charged macromolecules like albumin

HCV screen and diagnosis

Hep C: SCREEN with enzyme immunoassay (EIA), where presence of anti- HCV indications active infection or recovery Confirm with RIBA (recombinant immunoblot assay)- a specific test - HCV RNA viral load detected using PCR- use it to detect infection and monitor on antiviral therapy - Positive RIBA and positive HCV RNA = acute infection - Positive RIBA and negative HCV RNA= cured

Hepatic encephalopathy

Hepatic encephalopathy (also known as portosystemic encephalopathy) is the occurrence of confusion, altered level of consciousness, and coma as a result of liver failure.

Hep E

Hepatitis E is the cause of another form of hepatitis that is spread by the fecal-oral route and therefore resembles hepatitis A. Classically, contaminated water and uncooked seafood. Hepatitis E virus is a positive sense single-stranded RNA virus. Like hepatitis A, infection with this virus is frequently subclinical. When symptomatic, it causes only acute disease that may cause fulminate hepatitis to death, ESPECIALLY in pregnant women.

THE MAJOR CHARACTERISTICS OF NORMAL GLOMERULAR FILTRATION

High permeability to water and small solutes, because of the highly fenestrated nature of the endothelium. Impermeability to proteins - (glomerular barrier function) conferred by the visceral epithelial cell (podocyte).

Diabetes nephrooathy

High serum glucose leads to *nonenzymatic glycosylation (NEG)* of *renal vascular basement membrane*, resulting in it becomming leaky, protein leaks into wall of blood vessel leading to *hyaline arteriolosclerosis*, which *thickens blood vessel wall* which *decreases caliber of lumen*. There is preferential involvement of *Efferent arteriole* which creates a *backpressure* in the glomerulus which *increases glomerular filtration rate*. This initially presents as *microalbinuria* but eventually you get hyperfiltration damage which progresses to mesangial proliferation/sclerosis, which progresses to *nephrotic syndrome*. This is characterized by *↑ mesangial matrix* either in a *nodular pattern (nodular glomerulosclerosis, also known as *Kimmelstiel-Wilson disease)* or a *diffuse pattern (diffuse mesangial sclerosis)* Note: nodular formation due to deposition of type IV collagen (aka microangiopathy) More common in type I diabetics than type II. Widespread thickening and ↑ permeability of the glomerular basement membrane and renal tubular basement membrane → early disease presents with microalbuminuria Note: hyalinization of the afferent arteriole occurs later which eventually ↓ GFR

Type 1 IDDM signs/symptoms/diagnosis

High serum glucose: -fasting > 125mg/dL aka 7.0 mmol/l measured twice ... -.also 2hr plasma glucose ≥ 200 mg/dl aka 11 mmol/l during oral glucose tolerance testing: patient is given a 75g glucose load bolus. - HbA1c ≥ 6.5% is now part of the diagnostic criteria. -polydipsia, polyuria, polyphagia(excessive hunger) but weight loss

Papillary carcinoma histo

Histologically, cells are described as having "Orphan Annie eye nuclei" because of the characteristic shape they assume (white clearing in center of nucleus). - Another common histological finding is psammoma bodies (layered calcification). - Excellent prognosis.

Biopsy of hypertrophic cardiomyopathy

Histopathologically, tissue samples are characterized by *"myocardial disarray"* which includes disoriented, tangled, and hypertrophied myocardial fibers.

Type 1 HS

Hypersensitivity occurs when the body has an inappropriate, or exaggerated inflammatory response to generally benign stimuli. Common antigens include: pollen, dust, as well as food items such as peanut, shellfish. Initial antigenic exposure induces synthesis of IgE, which binds to the surface of mast cells and basophils via its Fc portion. This acts as a "primer" for stronger exponse with *repeat exposure* When re-exposed to *allergen*, there is cross linking of IgE and it *activates mast cell* when then immediately dumps *pre-formed histamine*, which causes histamine induced *vasodilation (arteriole)* and increase permeability (postcapillary venule) and prostglandins, etc. Note: These mediators are responsible for the immediate edema, erythema and pruritis that result after exposure. • While the initial phase is in progress, the *mast cell* also begins synthesizing *leukotrienes* C4, D4, E4 and their derivatives as a part of the late phase of the reaction to prepetuate inflammation by - vasoconstriction in blood vessels - increase vascular permeability - constrict smooth muscle of broncus The products of the late phase reaction are inflammatory and attract neutrophils and eosinophils.

Cretinism

Hypothyroidism in neonates and infants Presents as mental retardation, short stature, skeletal abnormalities, enlarged tongue, umbilical protrusion and hernia. Caused by: - maternal hypothyroidism during pregnancy - Thyroid agenesis (doesn't form thyroid) - dyshormonogenetic goiter (cannot produce thyroid hormone, most common deficient enzyme is thyroid peroxidase) - Iodine deficiency

Other complications of Neonatal RDS

Hypoxemia increases risk for persistence of *patent ductus arteriosus*.. *Pulmonary vasoconstriction* due to *hypoxia* in areas of atelectasis leads to *increased pulmonary vascular resistance*, which promotes *right-to-left shunting* and can lead to a * persistent patent ductus arteriosus.* and *necrotizing enterocolitis* (due to decreased O2 to gut). When patients given supplemental oxygen, it increases *free radical injury* risk. This gets into blood and affects *retina* (called *retrolental fibroplasia*(retinopathy of prematurity) induce VEGF and lead to abnormal proliferation of blood vessels. and can also cause blindness. Free radicals can also damage *lung* and cause *bronchopulmonary dysplasia*

HIV structure (and proteins)

Icosahedral capsid—enveloped, diploid (+) sense ssRNA lentivirus (a slow type of retrovirus): The 2 RNA strands are identical. Envelope consists of lipid bilayer. Has gp41 and gp120 glycoproteins. gp120 (major surface antigen) interacts with CD4 receptor. gp41 fuses viral envelope with target cell membrane. p24 is the group-specific antigen. Located in core. Antibodies to p24 → early serologic marker of infection.

eccentric cardiac hypertrophy

If the precipitating stress is volume overload, the ventricle responds by adding new sarcomeres in-series with existing sarcomeres (i.e., the sarcomeres lengthen rather than thicken). This results in ventricular dilation while maintaining normal sarcomere lengths - the heart can expand to receive a greater volume of blood. The wall thickness normally increases in proportion to the increase in chamber radius. This type of hypertrophy is termed eccentric hypertrophy.

Large cell carcinoma histopath summary

If we see *glands* or *mucus production* think *adenocarcinoma* If we see *keratin pearls or intracellular bridges* think *squamous cell carcinoma* If we don't see any of this, call it a *large cell carcinoma*

Which Igs can activate ADCC (antibody-dependent cell-mediated cytotoxicity)

IgG, IgE In IgG-mediated ADCC, the target cells are first bound by IgG → effector cells may then bind to the free Fc "tail" of IgG → effectors release cytotoxic mediators (e.g., lytic enzymes, perforin, granzymes, tumor necrosis factor) to ultimately kill the target cell. Note: phagocytosis is not involved in ADCC! Effector cells capable of IgG-mediated ADCC all have Fcγ (membrane receptors for the Fc region of IgG), and include: - NK cells - Neutrophils - Monocytes and Macrophages - Eosinophils

antibodies and compliment system

IgM and IgG can activate CLASSICAL complement pathway (IgM is more efficient) IgA is capable of activating the: - alternative pathway of the complement cascade - mannan-binding lectin pathway of the complement cascade

causes of malabsorption

Immunologic/allergy (ie, celiac) -Infection (ie, Whipple) - Crohns

hepatitis liver enzymes

In alcoholic hepatitis, AST > ALT, because alcohol damages mitochondria, which is where AST is normally located.

Primary hypertension

In primary or essential hypertension there is no obvious underlying cause, although many risk factors may be present. About 95% of cases. The etiology of essential HTN is *poorly understood*, but is related to: -Genetic factors, family history. -Increased angiotensin 2 -Small nephron number (congenital, injury, or genetic) The prevalence of HTN increases with age, smoking alcohol, high salt diets, obesity, diabetes, and inactivity

endometrial hyperplasia pathogenesis

Inactivation of the PTEN (phosphatase and tensin homolog) acts as a tumor suppressor gene through deletion and/or inactivation - (the key factor) . PTEN is involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly. Mutations of this gene contribute to neoplastic development.

Hyperthyroidism

Increased levels of circulating thyroid hormone - Increase BMR (by synthesis of Na/K ATPase!!!!) - Increased SNS activity (increased B1 receptor expression!!!)- - ↑ SNS → overstimulation of levator palpebrae superioris (a muscle which receives SNS innervation from the internal carotid plexus & contracts reflexively to elevate the upper eyelid) → wide-eyed staring gaze and lid lag.

Suppurative (Polymorphonuclear) Inflammation

Increased vascular permeability. Leukocytic infiltration, predominantly of neutrophils. The neutrophils are attracted to the site of infection Release of chemoattractants from the "pyogenic" bacteria. Neutrophils forms pus.

Delayed wound healing

Infection is most common cause. Vitamin C deficiency- proline and lysine residues of procollagen are hydroxylated with vitamin C, which allows crosslinking of procollagen. Copper deficiency- lysly oxidase requires copper as cofactor, necessary for collagen crosslinking Zinc deficiency- needed for collagenase Other causes: foreign body, ischemia, diabetes, malnutrition

Pneumonia

Infection of the *lung parenchyma*, occurs normally when normal defenses impaired. ie, impaired cough reflex, damage to mucociliary escalator (ie, virus), or mucus plugging.

Late phase of asthma

Inflammation from proteins such as *major basic protein* perpetuate broncho-constriction characterized by infiltration of tissues with eosinophils, neutrophils, basophils, monocytes, and CD4+ T cells as well as tissue destruction, typically in the form of mucosal epithelial cell damage.

Rhinitis

Inflammation of the nasal mucosa... *adenovirus* is most common cause. Allergic Rhinitis is due to type 1 HSR: (due to pollen which acts as antigen). Characterized by inflammatory infiltrate with eosinophils. Associated with other disorders like asthma and eczema. Repeated bouts of rhinitis lead to *nasal polyps*.

Glucocorticoids

Inhibit protein synthesis, stimulate protein catabolism - promote gluconeogenesis, glycogenolysis - anti-inflammation via reduced macrophages, decreased pro-inflammatory cytokines - decrease gene expression for genes incoding for COX

cortisol and immune suppression

Inhibits phospholipase A2, thus cannot form arachidionic acid metabolites, and subsequent inflammation 2) Inhibits IL-2 , important T-cell growth factor 3) Inhibits release of histamine from mast cells which is essential for vasodilation and vascular permeability

Nitrate signal mechanism

Initial metabolism of these drugs releases nitrite ions (NO 2−). Within the cell, NO2− is converted to nitric oxide (NO), which then activates guanylyl cyclase, causing an increase in the intracellular concentration of cGMP in the vascular smooth muscle cells. cGMP activates protein kinase G (PKG), an enzyme that causes the vascular smooth muscle to relax by several mechanisms. These include: (i) activation of Ca pumps that sequester Ca 2+ into the smooth endoplasmic reticulum (SERCA) and extrude Ca 2+ into the extracellular space (PMCA); and (ii) (ii) activation of K-channels, causing membrane hyperpolarization that inhibits Ca influx by switching off voltage-dependent Ca-channels. The fall in [Ca 2+ ] decreases MLCK activity, and relaxation occurs.

tissue Repair

Initial phase is granulation tissue (NOT same as granuloma) phase, with 3 major cell categories: 1) Fibroblasts (deposit type 3 collagen) 2) Capillaries (provide nutrients) 3) Myofibroblasts (contract wound) Eventually, granulation tissue progresses to a scar, with type 3 collagen (pliable) transition to type 1 (strong) collagen. Collagenase (!!) removes type 3 collagen and requires zinc(!!!) as a cofactor

urethra epithelial in male vs female

Initially, the urethra is lined by a transitional epithelium in males and females. In males, it is replaced by a pseudostratified or stratified columnar epithelium below the openings of the ejaculatory ducts . The distal parts of the female urethra and male urethra are lined by a stratified squamous epithelium.

Innate immunity

Innate immunity: includes many cellular and humoral devices, from nonspecific barriers (e.g., skin) to recognition and destruction of specific pathogens (e.g., complement-mediated opsonization of microorganisms for subsequent phagocytosis). • Innate immunity is maintained by a vast repertoire of serum proteins that recognize general classes of invading agents. This provides for a fast immune response; however the proteins do not exhibit any memory in the case of recurrent infection. • The innate immune system involves: - NK (natural killer) cells - Phagocytes, neutrophils - Dendritic cells - Complement

mesangium

Inner layer of the glomerulus, within the basement membrane surrounding the glomerular capillaries. These cells are phagocytic and secrete the amorphous basement membrane-like material known as the mesangial matrix. They are typically separated from the lumen of the capillaries by endothelial cells.

Subunit vaccines

Instead of the entire microbe, subunit vaccines include only the antigens that best stimulate the immune system Because subunit vaccines contain only the essential antigens and not all the other molecules that make up the microbe, the chances of adverse reactions to the vaccine are lower.

Type 1 IDDM

Insulin deficiency due to autoimmune INFLAMMATION OF ISLETS and viral destruction of beta cells by T Lymphocytes (Type 4 hypersensitivity). Autoantibodies to insulin can be seen in blood (even years before manifestation)

integrase inhibitors

Integrase inhibitors prevent the insertion of viral dsDNA into the host genome Raltegravir (first drug approved in this class)

IBD overview

Inflammation of the gastrointestinal tract that exists in two forms. (1) Crohn's disease (2) Ulcerative colitis

Thrombosis

Is defined as coagulated blood containing platelets, fibrin, and entrapped cellular elements, within a vascular lumen

Articular Cartilage

Is not surrounded by a perichondrium and is partly vascularised. The main source of nourishment for articular cartilage is the synovial fluid, which fills the joint cavity. Additional small amounts of nutrients are derived from blood vessels that course through the calcified cartilage close to the bone.

Hyaline cartilage

Is the most abundant type of cartilage. The matrix appears glassy → Hyaline Hyaline cartilage contains fibers made primarily of type II collagen only. Except in articular cartilage of joints, all hyaline cartilage is covered by a perichondrium. produced by chondrocytes

choriocarcinoma signs and spread

It becomes manifest only by irregular spotting of a bloody, brown, sometimes foul-smelling fluid. The titers of human chorionic gonadotropin are elevated to levels above those encountered in hydatidiform moles. Widespread metastases are characteristic: The lungs (50%) Vagina (30% to 40%) The brain Liver kidney.

Elastic cartilage

It's structure is very similar to that of hyaline cartilage. Type 2 collagen. but in addition to the other components, its matrix has: Elastic fibres Interconnecting sheets of elastic material. found in the: External ear, The walls of the external auditory canal, The eustachian tube,

Major Jones criteria

JONES - Joints—migratory polyarthritis - O—carditis (think of the "O" as the rough shape of the whole heart, including *all three layers*-endocardium, myocardium, pericardium), which may include endocarditis, myocarditis, and/or pericarditis. - Nodules (subcutaneous) on extensor surfaces (eg, wrist, elbow, knee)

K sparing diuretics

K sparing diuretics: 1. Aldosterone receptor antagonists — e.g., spironolactone, eplerenone 2. Na channel blockers — e.g., triamterene, amiloride

K-RAS

K-ras oncogene = on chromosome 12p12 K-ras oncogene is the Molecular "on/off" switch - recruits and activates proteins necessary for propagation of growth factor (Mutation = allows for polyp growth)

Kaposi Sarcoma

Kaposi sarcoma is a low grade, malignant endothelial cell proliferation malignancy that occurs most commonly on the skin but that can also occur in the mouth, GI tract, and respiratory tract. There are the following types: Kaposi sarcoma occurs most often in the *immunosuppressed* and is associated with *HHV-8* (!!) and *HIV*. Kaposi sarcoma is an AIDS-defining lesion and the *most common cancer in AIDS patients*

Aortic regurgitation complications

LV dilation (to accommodate the volume of the backflow without increasing filling pressure or left atrial pressure) and *eccentric* hypertrophy.

Anaplasia

Lack of differentiation is called anaplasia. Well-differentiated tumors - resemble the mature normal cells of the tissue of origin. Poorly differentiated or undifferentiated tumors - primitive-appearing and unspecialized cells.

Histiocytic and dendritic cell neoplasms

Langerhans cell sarcoma Follicular dendritic cell sarcoma Fibroblastic reticular cell tumor

*Large* elastic arteries blood supply

Larger (elastic) aa. require *their own* blood supply to function, and possess *vasa vasorum* within their *adventitial* layer. These *small vessels* supply oxygen and nutrients to the *outer layers of the thicker vessels* so that these regions do not have to rely on diffusion from the vessel lumen. Note: the infrarenal aorta does NOT have a vasa vasorum, so the outer layers of this region of the aorta must rely on diffusion of O2 and nutrients from the lumen of the aorta. In atherosclerotic disease, formation of plaques in the aortic wall greatly impede the diffusion of O2 and nutrients. The outer layers become weakened and increasingly compliant. Progressive dilation of the weakened aortic wall results in *abdominal aortic aneurysm*

Left heart failure symptoms

Left sided heart failure is generally said to be a *disease of symptoms* (rather than *signs like in RHF*) of *pulmonary congestion)!!!!*... the heart can't pump the blood forward, so it is *pumped backwards* and it piles up in vessels of lung This increases the *hydrostatic pressure* and leads to pulmonary edema Symptoms including: - dyspnea on exertion - orthopnea - paroxysmal nocturnal dyspnea. Fluid overload: the decreased cardiac output (less flow to kidney) causes an activation of *RAAS* system with retention of salt and water and *worsens* pulmonary congestion Symptoms of systolic and diastolic heart failure are indistinguishable from each other.

Anti-leukotrienes

Leukotrienes are inflammatory mediators that cause bronchoconstriction. Zileuton blocks conversion of arachidonic acid to leukotrienes. Zafirlukast and Montelukast block leukotriene receptors.

Loop diuretic sides

Like thiazide diuretics, loop diuretics are *potassium-wasting diuretics* and therefore have the potential to cause *hypokalemia and a metabolic alkalosis*. Because the resorption of calcium and magnesium requires functional NaKCC cotransporter activity, *hypomagnesemia* and *hypocalcemia* can occur. *Endolymph* uses an NaKCC cotransporter as well; blockage can prevent normal electrolyte balance in the ear, *causing ototoxicity*. ↑ serum levels of: - Uric acid (hyperuricemia) → may precipitate gout

Live, attenuated vaccines

Live, attenuated vaccines contain a version of the living microbe that has been weakened in the lab so it can't cause disease. Avoid in innunocombromised.

Cirrhosis and estrogen

Liver removes estrogen from blood. So, in cirrosis, excess extrogen leads to: Gyno Palmar erythema -Spider angioma (swollen blood vessels) found slightly beneath the skin surface, often containing a central red spot and reddish extensions which radiate outwards like a spider's web)... more than 5 of these may be liver disease Also increase SHBG which decreases free test.

APC gene

Located on chromosome 5q21 ! The APC gene is part of the *WNT/ β-catenin pathway* - APC acts as a "scaffold"- protein for β-catenin, which NORMALLY prevents it from entering the nucleus. APC gene mutation leads to *RISK* for *development of polyp* because of accumulation of β-catenin in the nucleus. This accumulation causes uncontrolled expression of *early response genes*, which produce *transcription factors* such as *MYC1* which drives the cell *into the cell cycle*, and activates *delayed response genes* such as *Cyclin D1*. It is a *tumor supressor gene* so you have to knock out *both copies* to develop the risk, somatically. But, it is possible to *INHERIT ONE bad copy*, this is *Familial adenomatous polyposis* syndrome.

Mallory-Weiss syndrome

Longitudinal esophageal mucosal tear at *GE junction* caused by *severe vomiting* . As vomit goes up, it creates a tear of the mucosa. Seen in Chronic alcoholics, bulimics (they vomit a lot). The tear leads to bleeding and *PAINFUL hematemesis* w/ associated pain. 75% of patients also have hiatal hernia Also has risk of *Boerhaave syndrome*.

Hyper-osmotic dehydration

Loss of hypotonic fluid from ECF (ie, diabetes insipidus, lack of water intake, mega sweating/exercise) ECF volume decreases, ECF osmolarity increases. So, there is a *fluid shift* from ICF to ECF to balance the osmolarity. ICF volume will decrease ICF osmolarity will increase

Osteoporosis

Loss of osteoid (organic bone matrix) but mineralization is normal.

Lung cancer categories:

Lung cancer can arise from any level of the airway and many forms have similar risk factors, presentation, diagnosis, and treatment. Divided clinically into: 1. small cell lung cancer (15%) 2. non-small cell lung cancer (85%), which includes : - adenocarcinoma (40%) - squamous cell carcinoma (30%) - large cell carcinoma (10%) - bronchoalveolar cell carcinoma. *small cell carcinoma* is usually treated with *chemo* first, not surgery... while *non-small* usually treated with *surgery first*

Normocytic anemia

MCV 80-100 - due to increased peripheral destruction OR underproduction, use reticulocyte count to help distinguish. Reticulocytes are larger than RBC's, has residual RNA, so bluish color on RBC smear. Normally reticulocyte count is 1-2% (of total red blood cells!!!) , in anemia, uncorrected reticulocyte count is > 3% (of total RBC's!!) b/c many RBC's get destroyed. Concentration of reticulocytes goes up, absolute number doesn't really. Correct reticulocyte count: multiply reticulocyte count% X patient Hct/45. Corrected reticulocyte count > 3% indicates good marrow response, suggests peripheral restruction (hemolysis). Corrected reticulocyte count <3% indicates poor marow response, suggests underproduction.

Macrocytic anemia overview

MCV > 100. Most commonly due to B12/folate deficiency (megaloblastic anemia), which are DNA precursors! → ↓ DNA synthesis → RBCs grow larger than normal before dividing - cell has ~1 less division (contrast to microcytic which has ~1 more division)

After neutrophils die

Macrophages enter, peak at 2-3 days after inflammation begins. They are derived from monocytes in blood, in tissue become macrophages. Come into tissue exact same way neutrophils do (margination, rolling, adhesion, transmigration)

Fever inflammation (!!)

Macrophages release IL-1 (!!) TNF... which hit perivascular cells of the hypothalamus which increase COX, this increases PGE2 to raise set point.

Diagnose Barett's

Made by endoscopic examination and biopsy (2 criteria): (1) Endoscopy → columnar epithelium lining the distal esophagus (replacing stratified squamous epithelium) (2) Histologic biopsy → the columnar epithelium shows specialized intestinal metaplasia (contains goblet cells)

Hb and microcytic anemia

Made of heme (iron and protoporphyrin) + globin - If low iron, there is microcytic anemia (iron deficiency anemia) - if Iron is locked away in macrophages because of chronic inflammation, it is low (anemia of chronic disease) - Any circumstance which decreases production of protoporphyrin (sideroblastic anemia) - decreased production of globin chain (thalassemia)

Define three factors which can interfere with good nutrition.

Maldigestion - inability to break down large molecules to small molecules Malabsorption- inability to transport molecules across the intestinal mucosa to circulation Malassimilation- (both)

Choriocarcinoma

Malignant neoplasm of trophoblastic cells derived from any form of previously normal or abnormal pregnancy. About 1 in 40 hydatidiform moles may be expected to give rise to a choriocarcinoma, in contrast to 1 in approximately 150,000 normal pregnancies.

Follicular carcinoma

Malignant proliferation of follicles surrounded by a fibrous capsule, BUT hallmark of follicular carcinoma vs adenoma is in carcinoma, invasion through/beyond capsules). - More common in females, and patients age 40-60. Second most common. Fine needle aspiration unfortunately cannot distinguish between follicular adenoma and carcinoma. Need to see capsule, so need to see gross specimin, or examine capsule under microscope to ensure no extension beyond capsule. - Propensity for hematogenous (blood) spread, thus can present with distant metastasis (liver, bone, lungs).

Hepatitis

Many people mistakenly think that hepatitis means viral hepatitis, and that all forms of hepatitis are contagious. Actually, the word hepatitis is a catch-all term that refers to any inflammation of the liver -- the irritation or swelling of liver cells from any cause. Hepatitis can be acute (inflammation of the liver that lasts less than six months) or chronic (inflammation of the liver that lasts more than six months) and has many different causes

mast cell activation

Mast cells (and basophils) are activated by the cross-linking of high-affinity IgE Fc receptors; in addition, mast cells may also be triggered by several other stimuli, such as complement components C5a and C3a (called anaphylatoxins because they elicit reactions that mimic anaphylaxis)

Back pain categories

Mechanical Inflammatory Metabolic Neoplastic referred

melanogenesis

Melanin is synthesized in the melanocyte via tyrosine, tyrosinase accumulates in melanocyte. 1. Melanin synthesis begins in the stage II melanosomes. 2. Melanin is accumulated and forms stage III melanosomes. 3. Loses tyrosinase activity and becomes melanin granule 4. Melanin granules migrate to melanocytes processes and transfered to keratinocytes

Pain ladder

Mild pain: simple analgesics (non-opioid) .. ie, paracetamol, conventional nSAIDs Moderate pain: Weak opioid (ie, hihydrocodeine) Severe pain: morphine Note for step 2 and 3, can give gabapentin as an adjuvant alalgesic.

Mitral Stenosis overview

Mitral stenosis is the narrowing of mitral valve due to *calcification or valvular damage* that results in an increase in left-atrial pressure, and an increased left-atrial-left-ventricular pressure gradient. Mitral stenosis results in increased left atrium pressures and pulmonary congestion. Almost all cases are *secondary to rheumatic heart disease*, which causes immune-mediated damage to the valve. This results in scarring and narrowing of the valve, causing *fusion of the commissures*, called a "fish mouth" valve.

Graves disease

Most common cause of hyperthyroid (85%).....Autoantibody (IgG) that stimulates TSH receptor - increase synthesis/release of thyroid hormone - classically occurs in child bearing age women - Is a type 2 hypersensitivity

Horseshoe kidney

Most common congenital renal anomality, right and left kidneys fuse (90% are fused at the inferior pole; 10% are fused at the superior pole) Horseshoe kidneys become *trapped under the inferior mesenteric artery* (at vertebral level L3) ∴ *remain low in abdomen* (as it *tries to ascend*) and may compress ureters, leading to urinary tract obstruction and possibly urinary stasis → ↑ incidence of UTIs and nephrolithiasis, but otherwise normal kidney function.

Describe common causes of abnormal uterine bleeding:

Most common is DUB from Endometrial Hyperplasia (anovulatory cycle) Adenomyosis Endometrial Carcinoma Leiomyomata Chronic endometritis with numerous plasma cells Endometrial polyp.

CLL presentation

Most common leukemia found in adults in the US. Patients usually male, > 60 years of age and experience an indolent clinical course, generally presenting with generalized painless lymphadenopathy. Mean survival 3 to 7 years.

ALL- Acute lymphoblastic leukemia

Most common malignancy in children, Note: (also associated with Down Syndrome AFTER the age of 5:... "mnemonic: we ALL fall DOWN") - also the most responsive to therapy There are 2 general types of ALL: B-ALL and T-ALL: (because the lymphoblast can either be a B-lymphoblast, or a T-lymphoblast)! Classification is based on surface markers. But BOTH have TdT (!!) The total number of white blood cells may be decreased, normal, or increased, but the number of red blood cells and platelets is almost always decreased. In addition, very immature white blood cells (blasts) are often present in blood samples examined under a microscope

causes of chronic renal failure and urinalysis

Most common primary causes of chronic renal failure are diabetes mellitus (40% of cases) and hypertension (30%), (note, Marian says they are secondary) Primary also includes Less common causes include chronic glomerulonephritis (15%), interstitial nephritis (5%), cystic renal disease (5%) Urinalysis: - Tubular dysfunction → isosthenuria (inability to concentrate or dilute urine) → fixed specific gravity, free water clearance = zero - Broad/waxy casts

B-ALL

Most common type of ALL B-ALL: -Presents as blood disorder, will generally metastasize to CNS -Surface Markers: CD10 (aka CALLA), CD19, CD20 and CD22 Excellent prognosis and response to chemotherapy, but it requires prophylaxis to scrotum and CSF (because the chemo does not cross blood-brain or blood-testicle barrier)

Hyperplastic polyps

Most common type, benign with NO malignant potential. has a "serrated" appearance. Usually arises in left colon (rectosigmoid).

Iron deficiency anemia

Most common type, due to decreased levels of iron. Iron is consumed in heme-form (meat) and non-heme-form (vegetables)... heme-form is more readily absorbed. Absorption occurs in duodenum (!!!), where enterocytes take it up, then transfer it into blood via ferroportin transporter. In blood, iron is bound to transferrin and delivers it to liver and bone-marrow macrophages for storage where it is stored as bound to ferritin.

Dilated Cardiomyopathy

Most common, accounts for 90% of cases. a progressive dilation of *all 4 chambers* of the heart that leads to decreased contractility and heart failure resulting from *systolic dysfunction*. This condition is also known as congested cardiomyopathy. Systolic dysfunction in dilated cardiomyopathy manifests as a *reduced ejection fraction* (<40%) and can be detected during physical exam as a *narrow pulse pressure* and *S3 heart sound* Dilated cardiomyopathy is characterized by *global enlargement* of the heart, which is visible with imaging.

Restrictive lung diseases due to

Most commonly due to *interstitial disease* of the lung... these are disorders where you get fibrosis of the *interstitium* *interstitium* is a collection of support tissues within the lung that incluces the alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues. Can also be due to *chest wall abnormalities* (ie obesity) Makes it difficult to get air in

Gastric ulcers

Most gastric ulcers are located on the *lesser curvature* of the *distal stomach*. Usually due to H-pylori (about 50-60% of gastric ulcers), other causes could be NSAIDs and "bile reflux" Presents as epigastric pain which gets worse immediately before or during a meal. Gastric ulcers carry the risk of rupturing the left gastric artery . Gastric ulcers are more likely to undergo malignant transformation to *gastric carcinoma* .. note that gastric carcinoma can also *create* ulcers. Benign ulcers are small, "punched out", and clear margins (no 'piling up' of edges).... malignant ulcers are larger, irregular, 'piling up' at edge'.

Myoglobin in MI

Myoglobin: primary oxygen carrying molecule in cardiac and other types of muscle (∴ *lacks specificity* for the heart). 1. Serum myoglobin levels *rise very quickly after an MI — vs. troponin and CK-MB*, which begin to rise a couple hours after an MI (this is why the levels of the so-called cardiac enzymes (troponin, CK-MB) are "trended".

Medications for angina

Nitrates, B-blockers , Ca2+ blockers (mostly prinzmetal angina to counteract the vasospasm) Note however, that none of these medications decrease the progression of CAD. Treatment of patients with CAD also should rely on the prevention of acute coronary syndromes using: Aspirin for anti-platelet effects Statin drugs for lipid lowering effects

Hashimoto thyroiditis presentation

Nontender thyroid, which often becomes diffusely enlarged → insidious development of hypothyroidism, most commonly in women age 30-50 Presents with all other signs of hypothyroidism

Anti-Thrombin III deficiency

Normally endothelial cells make heparin-like molecules which bind ATIII and activate them... ATIII then activates thrombin. If deficient, there is increases risk for formation of thrombus.

carcinomas spread

Normally like to spread to lymph nodes (!!!), EXCEPT (!!)for 4 carcinomas which like to spread to blood: 1) Renal cell carcinoma (renal vein) 2) Hepatocellular carcinoma (hepatic vein) 3) Follicular carcinoma 4) Choriocarcinoma

AAA presentation

Normally presents as a *pulsatile abdominal mass* that *grows* with time. The major complication of an abdominal aortic aneurysm is *rupture*!!. When it ruptures, it presents with a triad of - hypotension (because there is a bleed) - pulsatile abdominal mass - flank pain, usually localized to the left side (aorta is retroperitoneal on left side)

Sickle cell anemia

Normocytic anemia. HbS: β-globin gene point mutation at codon 6 causes normal glutamic acid (hydrophilic) to be replaced with valine (hyprophobic) Likely due to protective role against falciparum malaria. 2 abnormal β chains results in >90% HbS

11 hydroxylase deficiency

Note: Pregnenalone can be converted into 3 groups: 1) Mineralcorticoids 2) glucocorticoids 3) sex steroids 21 hydroxylase is needed for both mineral corticoids and glucocorticods 11 hydroxylase is needed for glucocorticoids, but it converts WEAK mineralcorticoids into strong mineralcorticoids.... so, 11-hydroxylase deficiency still leaves us some weak mineralcorticoids, may not get salt wasting (doesn't get hyponatermia, hyperkalemia, and hypovolemia.)

goals of anginal therapy (!!)

Objective of anginal therapy is to: - ↓ myocardial oxygen demand/consumption - and/or ↑ coronary blood flow. This can be achieved by: 1. ↓ HR (heart rate) 2. ↓ Contractility 3. ↓ Preload may help relieve Sxs of angina due to volume overload (eg, CHF) by improving the myocardial stretch potential on the Starling curve Note: preload ~EDV (end-diastolic volume); EDV, in turn, usually (but not always) correlates with EDP (end-diastolic pressure) 4. ↓ Afterload (mean arterial pressure, which is proportional to total peripheral resistance)

lungs and CF

Obstruction and infection of the air passages. The bronchioles are distended with thick mucus associated with marked hyperplasia and hypertrophy of the mucus-secreting cells. Superimposed infections give rise to severe chronic bronchitis and bronchiectasis . Staphylococcus aureus, Hemophilus influenzae, and Pseudomonas aeruginosa and opportunistic infections.

causes of postrenal AKI

Obstruction of urethra: - BPH (benign prostatic hyperplasia) = most common cause of postrenal AKI - Nephrolithiasis (kidney stones in urethra or impacted at bladder neck) Obstruction due to neoplastic invasion/extension (eg, neoplasia of cervix, prostate, bladder) Bilateral obstruction of ureters (eg, retroperitoneal fibrosis—ureters are retroperitoneal structures) Bilateral obstruction of kidneys (eg, bilateral staghorn stones)

Chronic Endometritis

Occurs in patients with: Chronic PID Intrauterine contraceptive devices. Tuberculosis. (rare in Western countries). Presentation: Abnormal/Irregular bleeding Pain Discharge infertility

neurogenic claudication

Often associated with lumbar stenosis, pathophysiology is thought to be ischemia of the lumbosacral nerve roots secondary to compression from surrounding structures, hypertrophied facets, ligamentum flavum, bone spurs. dermatomal pain/weakness of ass, hip, thigh, leg. The pain is classically relieved by a change in position or flexion of the waist and not simply relieved by rest, as in vascular claudication. Therefore, patients with neurogenic intermittent claudication have LESS DISABILITY in climbing steps, pushing carts and cycling

oligohydramnios consequences

Oligohydramnios fails to provide the fetus with adequate amniotic fluid necessary to *fully mature the lungs* which leads to *pulmonary hypoplasia*→ severe respiratory failure and early neonatal death. oligohydramnios allows *compression of the fetus* within the uterus → *multiple deformations* (extrinsic disturbances of development): - *Facial deformities*: Potter facies—flattened "parrot beak" nose, low-set ears, micrognathia (recessed chin) - Limb deformities: rocker-bottom feet, club feet (talipes equinovarus)

open vs closed reduction

Open reduction refers to the method wherein the fracture fragments are exposed surgically by dissecting the tissues. Closed reduction refers to manipulation of the bone fragments without surgical exposure of the fragments. Once the fragments are reduced, the reduction is maintained by application of casts, traction or held by implants which may in turn be external or internal.

types of fractures

Open(compound)- breaks skin (closed doesn't) Comminuted- Greenstick Impacted Pott

Opioids receptors

Opioids act on three major membrane receptors throughout both the CNS, PNS as well as in the gastrointestinal system. The opioid receptor families are designated mu (μ), kappa (k), and delta (δ)......The analgesic effects of opioids occur primarily through μ receptors. opioid receptors are prominent members of the G protein-coupled receptors. Activation of opioid receptors leads to inhibition of adenylyl cyclase and a decrease in the concentration of cAMP, an increase in K + conductance, and a decrease in Ca 2+ conductance . These actions cause both presynaptic inhibition of neurotransmitter release (SUBSTANCE P) from the central terminations of small-diameter primary afferent fibers and postsynaptic inhibition of membrane depolarization of dorsal horn nociceptive neurons

Heart failure changes

Overall, the changes in cardiac function associated with heart failure result in a decrease in cardiac output.!!! This results from a decline in stroke volume that is due to systolic dysfunction, diastolic dysfunction, or a combination of the two. Briefly, systolic dysfunction results from a loss of intrinsic inotropy (contractility), due to alterations in signal transduction mechanisms, or from the loss of contracting muscle as occurs following acute myocardial infarction. Diastolic dysfunction refers to the diastolic properties of the ventricle and occurs when the ventricle becomes less compliant (i.e., "stiffer"), which impairs ventricular filling. Both systolic and diastolic dysfunction result in a higher ventricular end-diastolic pressure, which serves as a compensatory mechanism by utilizing the Frank-Starling mechanism to augment stroke volume Neurohumoral responses include activation of SNS and the RAAS, and increased ADH and ANP. The net effect of these neurohumoral responses is to produce arterial vasoconstriction (to help maintain arterial pressure), venous constriction (to increase venous pressure), and increased blood volume. In order to compensate for reduced cardiac output during heart failure, feedback mechanisms within the body try to maintain normal arterial pressure by constricting arterial resistance vessels through activation of the sympathetic adrenergic nervous system, thereby increasing systemic vascular resistance In heart failure, there is a compensatory increase in blood volume that serves to increase ventricular preload and thereby enhance stroke volume by the Frank-Starling mechanism

causes of ectopic pregnancy

PID - Fertility drugs (clomid) - use of an IUD - increasing age

endometrial carcinoma risk factors

PTEN mutation (also K-RAS, p53) obesity HTN unopposed estrogen

RF and heart morphology

Pancarditis - If the three layers are affected Pericardium, the inflammation is accompanied by a fibrinous or serofibrinous pericardial exudate ("bread-and-butter" pericarditis), which generally resolves without sequelae. The myocardium - (myocarditis) scattered Aschoff bodies within the interstitial connective tissue, often perivascular. Leaflet thickening, commissural fusion and shortening, and thickening and fusion of the tendinous cords.

Carb enzymes

Pancreatic amylase splits into smaller fragments.... alpha-dextrinase in brush border clips off glucose one at a time Disaccharides- Sucrase (sucrose into glucose plus fructose) Lactase (lactose into glucose and galactose) Maltase (into glucose)

Papillary carcinoma

Papillary Carcinoma: > 80% of thyroid cancer cases - Common in women, particularly in their 20s or 30s, especially those who have been exposed to ionizing radiation in childhood (ie, radiation for severe acne). - Propensity for lymphatic spread, thus can present with lymphadenopathy.

thyroid parafollicular cells (C cells)

Parafollicular cells: synthesize and secrete hormone calcitonin, which *inhibits osteoclasts* Medullary thyroid cancer originates from parafollicular (C cells) of the thyroid

Small cell carcinoma paraneoplasic syndrome

Paraneoplastic syndromes associated with ACTH and ADH production are common with small cell carcinoma. Cushing's syndrome and a Cushingoid body habitus can develop with excessive ACTH secretion. Electrolyte abnormalities such as hyponatremia can result due to SIADH. *Lambert-Eaton myasthenic syndrome*, which is a disorder of *muscle weakness* due to auto-antibodies directed against neuronal *pre-synaptic calcium channels*, can also be seen as a manifestation of small cell lung carcinoma.

erection

Parasympathetic nerve fibers release nitric oxide in addition to cAMP - NO activates guanylyl cyclase, increasing cGMP, which relaxes arteries of penis and smooth muscle fibers in erectile tissue of corpus cavernosum and spongiosum

Anemia of chronic disease pathophys

Pathophysiology of anemia of chronic disease is related to the persistent release of inflammatory mediators. HEPCIDIN, a liver peptide hormone that strongly regulates iron, is high in inflammation because Inflammatory state → IL-6 production which - ↑ hepcidin. Hepcidin 'locks' iron into storage sites, which limits iron transfer from macrophages in bone marrow, so we have impaired production of heme (despite the fact that iron stores are in fact adequate) Hepcidin also suppresses EPO production.

lung cancer presentation

Patients present with general, non-specific symptoms of pulmonary disease, such as cough, dyspnea, wheezing, obstruction, hemoptysis, and recurrent or severe pneumonia secondary to airway obstruction or tissue destruction. May have fatigue, anorexia, and weight loss. Disease is often advanced at presentation. Patients may already have metastatic disease or severe complications, such as superior vena cava syndrome.

GERD presentation

Patients typically complain of: - Heartburn and left upper quadrant or epigastric pain radiating into the neck. (Can sometimes present with severe chest pain, mimicking acute coronary syndromes.) - difficulty swallowing (dysphagia) or sometimes a sour taste in the back of their mouth associated with food. -*adult onset* asthma and cough (as acid shoots up, it irritates airway) Sx typically occur after large/fatty meals → commonly *aggravated by lying down/bending over* & alleviated by antacids

CF complications

Patients with CF have excessive production of thick, sticky mucus, which obstructs airflow in the small airways and alveolar ducts, not only making breathing difficult but also allowing bacterial infection and inflammation to occur. In response, white cells (neutrophils) are recruited to fight infection in the lungs. White cells migrate into the infected area, die, and release elastase and their DNA into the mucus, which further thickens the mucus. Patients with CF cough frequently and require daily chest and back clapping to dislodge the mucus from the plugged airways. Pancreas damaged. In addition to the pancreas, CF also affects the reproductive organs, causing infertility in almost all males and some females. Male infertility occurs because the vas deferens are either absent or underdeveloped. In the female, fertility is reduced because of irregularity in the menstrual cycle.

HCV treatment

Pegylated interferons (PEG-IFNs). Trials of PEG-IFN in combination with ribavirin have established its safety and efficacy. Combination therapy with IFNα and ribavirin is the current treatment of choice for patients with evidence of chronic hepatitis due to hepatitis C. Criteria for initiating treatment are controversial, but most physicians would initiate treatment in a patient with abnormal liver histology and elevated liver enzymes.

Peptic ulcer disease

Peptic ulcers are *deep mucosal lesions* that disrupt the muscularis mucosa coat of the *gastric* OR *duodenal* wall. Most ulcers (90%) involve the *proximal duodenum* (aka *duodenal bulb*) Most gastric ulcers are located on the *lesser curvature* of the *distal stomach*. PUD is most often caused by a Heliobacter pylori (H. pylori) infection (80-90% of the time). Non-steroidal anti-inflammatory drugs (NSAIDs) are the second most common cause of PUD.

peripheral nervous system

Peripheral nervous system All the nervous tissue lying outside the brain and spinal cord. It consists of 12 pairs of cranial nerves and 31 pairs of spinal nerves. Somatic nervous system Supplies motor fibers to skeletal muscles that are under conscious control Autonomic nervous system (ANS) Functioning largely below the level of consciousness Supplies sensory (afferent) and motor (efferent) fibers to smooth muscle, cardiac muscle, and glands. The ANS consists of Sympathetic (thoracolumbar) nervous system Parasympathetic (craniosacral) nervous system.

Pernicious anemia

Pernicious anemia: anti-IF (intrinsic factor) antibodies bind and thereby prevent IF (produced by parietal cells lining the stomach) from binding with vitamin B12 → ↓ absorption of vitamin B12 in the ileum → B12 deficiency → defective DNA synthesis → Megaloblastic macrocytic anemia: Neurologic deficits: B12 deficiency → defect in synthesis of CNS myelin → subacute combined degeneration due to demyelination of: - Dorsal columns (cuneate and gracile nuclei and tracts) → impaired position/vibration sense (positive Romberg test) - Lateral corticospinal tracts → signs of upper motor lesion (hyperreflexia, ↑ muscle tone, positive Babinski with toes upgoing/extending and fanning out upon stimulation of plantar aspect of foot) - Spinocerebellar tracts → ataxic gait

Acute Chorioamnionitis

Placental infections derived from ascending and blood-borne routes. On gross examination, the placenta contains greenish opaque membranes. Premature and/or prolonged rupture of fetal membranes increases the risk for intrauterine infection. This leads to acute inflammation of the fetal membranes. The fetus may become infected and suffer intrauterine fetal demise. The inflammation may lead to premature labor and premature birth.

Multiple Myeloma bones

Plasma cells and/or tumor cells produce osteoclast activating factor (OAF) !!! which activate RANK receptor on osteoclasts, and the osteoclasts are activated and they eat at bone which results in LYTIC, punched out lesions (particularly in vertebrae and skull... also ribs, pelvis). This results in bone pain, hypercalcemia, and increases risk of fracture. Hypercalcemia leads to: - lethargy, weakness - confusion - constipation

Multiple Myeloma Ig chain formation

Plasma cells overproduce Ig Light chain... normally plasma cell produces equal amount heavy and light.... this results in free light chain which circulates in the serum, and deposits in tissue, this is called PRIMARY (AL) amyloidosis. The free light chain is also excreted in the urine (a proteinuria), and this proteinuria is called Bence-Jones proteins!! The light chains can also deposit in the kidney tubules and lead to risk for renal failure ( This causes renal insufficiency → 2nd most common cause of death.)

SLE autoantibodies formed against

Plasma proteins (complement components, clotting factors) Protein phospholipid complexes (antiphospholypid Ab) They exert a procoagulant effect in vivo causing recorrent thrombosis miscarriages and cerebral ischemia Cell surface antigens (lymphocyte, neutrophils, platelets, erythrocytes) Intracellular cytoplasmic components (microtubles, lysosomes, ribosomes) Nuclear DNA, ribonucleoproteins and histones NOTE: SLE is mostly type 3 HS (immune complex) but some type 2 cytotoxic)

Post pardum blues

Post Partum Blues - it is very common for women to experience mood alterations in the 2 weeks post partum, including rapidly fluctuating mood, tearfulness, irritability, and anxiety are common symptoms • Symptoms peak on the fourth or fifth day after delivery and last for several days, but they are generally time-limited and spontaneously remit within the first 2 postpartum weeks. Symptoms do not interfere with a mother's ability to function and to care for her child.

Post renal azotemia

Postrenal azotemia (postrenal AKI): obstruction of urine outflow, kidneys are intrinsically normal Postrenal AKI = least common cause of AKI Results in a *backpressure* which *decreases GFR.*,... this also causes *azotemia* and *oligourea* In *early stage*, increased tubular backpressure *forces* BUN into the blood, so serum *BUN:creatinine > 15*... AND tubular function remains intact (FENa < 1% and urine osm > 500) But *long standing obstruction* leads to *tubular damage*, and since we need functioning tubules to resorb BUN, we have a *decreased resorption of BUN:creatine < 15* !! Also, we *cannot resorb sodium (FeNa >2%) * or we *cannot concentrate urine *urine osm > 500*)

ace inhibitors pregnancy

Pregnancy is a contraindication because the fetus requires a functioning RAA axis for renal development, and ACE inhibitor use is associated with *fetal renal agenesis*.

FSH function

Prepares the follicle of the month 2. Increases aromatase synthesis in the granulosa cells 3. Increases the synthesis of LH receptors

hyperaldosterone

Presents as HTN due to effects of aldosterone: -Principal cell grabs Na+, and dumps K+ -a-intercalated cell dumps H+ hypernatremia, hypokalemia, metabolic alkalosis.

Hodgkin lymphoma presentation

Presents as an acute infection: diaphoresis, pruritus, leukocytosis and localized nontender lymphadenopathy. Also "B" symptoms: fever, night sweats, weight-loss (from cytokines) Lymphadenopathy is most commonly above the diaphragm (80%) → cervical, supraclavicular or axillary regions On imaging: a mediastinal mass (mediastinal lymphadenopathy) is a common finding

A2 agonists usage and sides

Previously used to treat hypertension (although *methyldopa* is sometimes still used in the *pregnant hypertensive patient*); now *clonidine* is mostly used in treatment of *opioid withdrawal* because *sympathetic surges* are responsible for some of the side effects.

name the nephrotic syndromes

Primary (idiopathic) nephrotic syndromes - Minimal change disease - Focal segment glomerulosclerosis - Membranous nephropathy (membranous glomerulopathy) - MPGN (membranoproliferative glomerulonephritis)

HIV phases

Primary HIV infection This stage of infection lasts for a few weeks and is often ccompanied by a short flu-like illness. During this stage there is a large amount of HIV in the peripheral blood and the immune system begins to respond to the virus by producing HIV antibodies and cytotoxic lymphocytes. This process is known as seroconversion. If an HIV antibody test is done before seroconversion is complete then it may not be positive. STAGE 2 : Clinically asymptomatic stage. This stage lasts for an average of ten years and, as its name suggests, is free from major symptoms, although there may be swollen glands. The level of HIV in the peripheral blood drops to very low levels but people remain infectious and HIV antibodies are detectable in the blood, so antibody tests will show a positive result. Research has shown that HIV is not dormant during this stage, but is very active in the lymph nodes. A test is available to measure the small amount of HIV that escapes the lymph nodes. This test which measures HIV RNA (HIV genetic material) is referred to as the viral load test. STAGE 3 : Symptomatic HIV infection Over time the immune system becomes severely damaged by HIV. This is thought to happen for three main reasons: - The lymph nodes and tissues become damaged or 'burnt out' because of the years of activity; - HIV mutates and becomes more pathogenic. - The body fails to keep up with replacing the T helper cells that are lost. Symptomatic HIV infection is mainly caused by the emergence of certain opportunistic infections that the immune system would normally prevent. This stage of HIV infection is often characterised by multi-system disease and infections can occur in almost all body systems. STAGE 4 : Progression from HIV to AIDS As the immune system becomes more and more damaged the individual may develop increasingly severe opportunistic infections and cancers, leading eventually to an AIDS diagnosis.

Curvatures of spine

Primary curvatures (present at birth) are Thoracic, Sacral ... Cervical forms with head lifting, lumbar with standing/walking. Kyphosis is an exaggeration of the thoracic curvature (backwards), which may occur in the aged due to osteoporosis of disc degeneration. Lordosis (forward) is an exaggeration of the lumbar curvature, which may occur as a result of pregnancy, spondylolisthesis, or "potbelly." Scoliosis is a complex lateral deviation/torsion, which may occur due to poliomyelitis, a short leg, or hip disease.

Etiologies of hypothyroidism

Primary hypothyroidism: - Hashimoto thyroiditis (chronic autoimmune thyroiditis) - Post ablation: Surgical or I-131 radiation - Iodine deficiency - Drugs: Lithium, Amiodarone, Sulfonamides - Subacute lymphocytic thyroiditis (painless) Secondary hypothyroidism is caused by pituitary hypofunction. Tertiary hypothyroidism is caused by hypothalamic hypofunction.

Primary vs secondary adrenalcortical insufficiency

Primary: aka Addison's: Absence of hormone production in all 3 cortical divisions. Result is hyponatremic volume contraction, hyperkalemia, constipation, diarrhea, fatigue and skin hyperpigmentation Secondary: Decreased production of pituitary ACTH Diagnosis: No hyperpigmentation with decreased ACTH, but increased cortisol response to ACTH. Contrast with Primary (Addison's disease) which has hyperpigmentation with increased ACTH

primordial vs primary follicle

Primordial- primary oocyte and one layer of follicular cells primary- follecular cells form a layer of cuboidal cells, then granulosa cells. Follicle then grows and the *antrum* is formed, so follicles are them called *secondary aka antral* follicles

Seminal vesicle

Produce a viscid secretion containing spermatozoa-activating substances. Constitutes 60-70 % of the ejaculate. Fructose, prostaglandins, citrate, proteins The compounds released by the seminal vesicles in addition to fructose has three main functions: 1) The formation of the sperm coagulum 2) The regulation of sperm motility 3)The suppression of immune function in the female genital tract.

- What is the endocrine function of the placenta?

Progesterone: By the end of the 4th month the placenta produces progesterone - sufficient to maintain pregnancy if the corpus luteum is removed/fails to function properly. • Hormones synthesised in the syncytial trophoblast. Produces increasing amounts of estrogenic hormones - estriol predominantly - until just before end of pregnancy when a max level is reached. • These high levels of oestrogens stimulate uterine growth and development of the mammary glands. hCG: • Somatomammotrophin (hPL) - Growth hormone like substance. - Gives foetus priority on maternal blood glucose and makes mother diabetogenic - Promotes breast development for milk production.

B-ALL prognosis

Prognosis is based on cytogenetic abnormalities: More common one (especially in kids) is t(12;21... think '12 flipped') which has good prognosis t(9;22) has poor prognosis, more commonly seen in adults. Remember, the 9;22 translocation (Ph+, called Philidelphia!!) is commonly seen in CML, but it is also seen here.

pubarche

Puberty involves 2 endocrinological events: adrenarche and gonadarche o The increase in adrenal androgen secretion induces pubarche; o The appearance of pubic hair. This may be accompanied by axillary (armpit) hair growth. o Pubarche is considered precocious/premature if it occurs before 8 years of age in girls and 9 years of age in boys. o The increase in adrenal androgens may also be associated with comedonal (non-scarring) and inflammatory acne. Gonadarche • Is the activation of gonadal sex steroid production • It occurs several years after adrenarche. • The activation of gonadal sex steroid synthesis and secretion is dependent on the release of hypothalamic GnRH. • This then acts on the pituitary to cause the release of the gonadotrophins (LH and FSH). • Gonadotrophins act on the gonads to stimulate steroidogenesis.

Posterior pituitary

Release ADH, Oxytocin (made in hypothalamus) ADH functions: 1) Moderate vasoconstriction 2) Antidiuretic effect, increases passive water reabsorption in renal collecting ducts Oxytocin functions: 1) Cervical distension causes activation of the SON and PVN, promoting oxytocin synthesis and release. Oxytocin in turn stimulates cervical, vaginal distention and uterus contraction 2) Letdown reflex: In lactating (breastfeeding) mothers, suckling causes pituitary to secrete oxytocin, which acts at the mammary glands, causing milk to be 'let down' into subareolar sinuses, from where it can be excreted via the nipple. 3) MAY be involved in process of enchancing sperm migration in fertilization SON and PVN axons terminate in the Posterior pituitary,their axon terminals are called Herring bodies

Colorectal cancer location.

Remember the phrase: "Left side obstructs, right side bleeds." Right sided tumors tend to grow as *raised lesion*, commonly present with fatigue and weakness due to *iron deficiency anemia* due to *bleeding* Right sided is more associated with *micosatellite instability* pathway. Left sided tumors commonly present with a *napkin ring lesion*, as lumen gets narrowed.... there is a change in bowel habits (thin stools), left lower quadrant pain or occult bleeding. FAP is more in *left side*

Arteriole resistance

Resistance of the arterioles is regulated by the sympathetic division of the autonomic nervous system. NE action on *α1-adrenergic* receptors (skin, splanchnic, renal)* induces vasoconstriction*, while NE action on *β2-adrenergic receptors* (in skeletal muscle arterioles) induces *vasodilation*

Type 3 collagen

Reticulate fibers in skin, blood vessels, granulation tissue, fetal tissue... it is Pliable. Aneurysms which can occur in EDS because type III collagen comprises blood vessels → weakening of vessel wall → aneurysm formation Ehlers-Danlos Syndrome: Vascular subtype → easy bruising, aortic dilation and dissection.

Comparison of the four major forms of vegetative endocarditis.

Rheumatic heart disease (RHD) - is marked by small, warty vegetations along the lines of closure of the valve leaflets. Infective endocarditis (IE) is characterized by large, irregular masses on the valve cusps that can extend onto the chordae Nonbacterial thrombotic endocarditis (NBTE) typically exhibits small, bland vegetations, usually attached at the line of closure. One or many may be present Libman-Sacks endocarditis (LSE) has small or medium-sized vegetations on either or both sides of the valve leaflets.

Right heart failure

Right heart failure (RHF): "backward" failure, meaning *right ventricle cannot pump blood* from the *venous system into the lungs*, causing blood to accumulate behind it. *Most common cause of RHF is LHF.* Other causes: - cor pulmonale - left-to-right shunt - tricuspid valve regurgitation

RHF signs

Right sided heart failure is generally said to be a *disease of signs* (rather than symptoms like in LHF) of venous congestion including - painful hepatosplenomegaly (may lead to cirrhosis. : due to venous congestion of hepatic veins of the liver. If severe enough, can cause portal hypertension and ascites..... Ascites, though a main feature of liver disease, may also be a sign of right-sided heart failure. - peripheral edema (increase in venous hydrostatic pressure accumulating in dependent areas) - jugular venous distension ( increased venous pressure in the superior vena cava → increased pressure of jugular vein)

right vs left murmurs and inspiration

Right-sided murmurs and abnormal heart sounds have increased intensity on inspiration. This is due to the increase in negative intrathoracic pressure drawing blood out of the venous system into the right side of the heart, hence accentuating the murmur and abnormal heart sound on that side. In contradistinction, left-sided heart murmurs and abnormal heart sounds do not change their intensity with deep held inspiration

Osmotic damage diabetes

Schwann cells take up glucose (without insulin), and aldose reductase converts it to sorbitol leading to osmotic damage.... since Schwann cells myelenate PNS, this caused a demyelenation is responsible for peripheral neuropathy (loss of sensation in distal extremities, also pressure ulcers). - Autonomic nerves may also be damaged → autonomic neuropathy → bladder and/or bowel incontinence, impotence Pericytes of retinal blood vessels take up glucose without insulin, aldose reductase converts to sorbital, causing osmotic damage and death of pericytes, which weaken blood vessel walls causing a retinal aneurysm which can rupture. Glucose to lens, convert to sorbitol by aldose reductase, cause cataract.

Inactivated vaccines

Scientists produce inactivated vaccines by killing the disease-causing microbe with chemicals, heat, or radiation. Such vaccines are more stable and safer than live vaccines: The dead microbes can't mutate back to their disease-causing state. Most inactivated vaccines, however, stimulate a weaker immune system response than do live vaccines. So it would likely take several additional doses, or booster shots, to maintain a person's immunity.

sertoli cells secrete what

Secrete two hormones - inhibin and activin - which provide positive and negative feedback on FSH secretion from the pituitary Production of AMH (Anti-Mullerian hormone) during embryonic development adjacent sertoli cells form blood-testes barrier

Vasoactive intestinal peptide

Secreted by many cells throughout GI tract and pancreas. induces glycogenolysis and hyperglycemia, stimulates GI fluid secretion and causes secretory diarrhea. Stimulates heart. Lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gall bladder. Also regulates CFTR gene, causing increased chloride secretion.

Beta blockers

Selective B1, or non-selective. β 1 -receptor stimulation increases contractility (inotropy), heart rate (chro- notropy), and AV conduction: whereas β 2 -receptor stimulation dilates the bronchial tree and causes peripheral vasodilation. *β1 blockade* then cause: ↓ HR (heart rate) ↓ AV node conduction velocity ↓ Contractility *β2 blockade is less clinically useful because preventing bronchial dilation is not helpful, although preventing cerebral vasodilation makes β2 blockade attractive for migraine headache prophylaxis.* Therefore, most beta blockers in use are *β 1 selective*. The most important *anti-anginal effect* is a *↓ in afterload*:

Sensory innervation of tongue

Sensory innervation to the tongue is provided by four nerves: lingual nerve chorda tympani glossopharyngeal nerve (cranial nerve IX) internal laryngeal nerve.

ACE inhibitor side effects

Side effects: - Impaired bradykinin metabolism by ACE → ↑ bradykinin levels → dry cough, angioedema - ↓ Angiotensin II → ↓ aldosterone release → hyperkalemia - ↓ Angiotensin II → less constriction of efferent arterioles → ↓ GFR → up to 30% ↑ in serum Cr is expected in most patients within 2-5 days of initiating ACE inhibitor therapy. Note: ACE inhibitors can precipitate *acute renal failure* in patients who *depend* on *efferent arteriolar* constriction to maintain GFR—eg, hypovolemia, decompensated heart failure, renal artery stenosis, chronic kidney disease.

Nephritic syndrome

Signs and symptoms of nephritic syndrome are all due to *inflamed, damaged glomeruli* → 1) Hematuria: - Patients often report "smoky" or "tea-colored" or "cola-colored" urine - 4+ blood on urine dipstick - RBC casts (in shape of tubules) on urinalysis. 2) Mild to moderate proteinuria—usually <1g/day (>150mg/day but <3.5g/day) ↓ GFR, yet renal tubular function (concentrating ability) is still intact → 3) Oliguria 4) ↓ Clearance of BUN, Cr, and uremic toxins → Azotemia (↑ BUN and ↑ serum Cr) with BUN:Cr ratio >15 5) Salt retention → Mild to moderate hypertension 6) Salt retention → *Periorbital edema* (around eyes...sometimes more generalized pitting edema may occur, but usually only in severe cases)

folate deficiency symptoms and seen in

Similar to B12 deficiency in presentation, except there are NO neurological symptoms.!!!! Commonly seen in: -Alcoholics -Pregnancy -Celiac sprue -Giardiasis -Phenytoin use -Chemotherapeutic agents (e.g. methotrexate) -TMP-SMX (TMP is a dihydrofolate

chronic bronchitis patients are called what?

Since hypoxia occurs early in the clinical course, patients with chronic bronchitis are referred to as "Blue Bloaters." !!

Smokers and emphysema

Smokers bring in a ton of garbage into lung, and is *chemotactic* to neutrophils and macrophages, and causes inflammation. Neutrophils release granules containing *proteases* → destroy the elastic tissue of the alveolar septa. Nicotine and smoke derived free radicals cause accumulation of PMNs and macrophages in the alveoli, which also *release proteases* which result in tissue damage. Smoking also enhances macrophage *elastase activity*, which is not susceptible to cleavage by α1-antitrypsin. Additionally, smoking derived free radicals can disrupt the balance between proteases and anti-proteases by *inactivating α1-antitrypsin* → "functional" α1-antitrypsin deficiency.

Airway remodeling in asthma

Smooth muscle hypertrophy is considered one of the common reactive changes associated with asthma. Submucosal gland hypertrophy → mucous plugging Sub-basement membrane fibrosis as a result of collagen deposition ↑ vascularity Inflammatory infiltration most commonly with eosinophils Squamous metaplasia is seen. Goblet cell hyperplasia. airway narrowing

carcinoma precursor lesions

Squamous dysplasia and carcinoma in situ Atypical adenomatous hyperplasia Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.

Squamous cell carcinoma (lung)

Squamous, Smoker, Sentral. classically associated with a *central location* of origin, arising from the segmented bronchi. (Think about where smoke goes when inhaled). However, squamous cell carcinoma of the lung is now frequently being seen in the periphery as well. Squamous cell carcinoma of the lung is more common in males, arises centrally, and is strongly associated with smoking. *most common* tumor in male smokers

astrocytes

Star-shaped cells with many long processes The largest and most numerous cells in the brain and spinal cord. 50:1 (astrocytes:neurons) They provide some degree of mechanical integrity to tissue They regulate/maintain the composition of ECF. Secretion or removal of neurotransmitters and their metabolism.

Central tolerance in bone marrow

Stem cell generated in the marrow, becomes: - immature B-cell in marrow - exits bone marrow as *naive mature B cell* as cell progresses from stem cell to immature B-cell, it expresses Ig, and *negative selection* question is asked "do they bind self antigen too tightly??* Dendritic cells in marrow have self antigen. If bind too tightly, cells either: 1) undergo receptor editing. - RAG genes will be re-expressed, which edits the light chain with the hope it will no longer bind self antigen, then go into periphery. 2) apoptosis

stenosis vs insufficiency

Stenosis The failure of a valve to open completely, which impedes forward flow. Generally, leading to pressure overload of the heart Insufficiency Results from failure of a valve to close completely, thereby allowing reversed flow. Generally leading to volume overload of the heart.

steroid hormone synthesis/action

Step 1 Steroid (or thyroid) hormone diffuses across the cell membrane and binds to its receptor. Step 2 The hormone-receptor complex enters the nucleus and dimerises. Step 3 The hormone-receptor dimmers are transcription factors that bind to steroid-responsive elements (SREs) of DNA. Step 4 DNA transcription is initiated. Step 5 New messenger RNA is produced, leaves the nucleus, and is translated to synthesize new proteins. Step 6 The new proteins that are synthesized have specific physiologic actions. For example: • Aldosterone induces the synthesis of Na+ channels in the renal principal cells.

Baroreceptor response

Stretch receptors located within the walls of the *carotid sinus* and aortic arch respond to both MAP and pulse pressure. Carotid sinus baroreceptors are tonically active, so increased activity indicates an increase in BP, and decreased firing indicates decreased arterial pressure . Changes in firing rate at the: - 1) carotid sinus (transmitted by CN IX) and at the : 2) aortic arch (transmitted by CN X) are relayed to the vasomotor center of the brain stem and elicit an ANS response. For example, decreased firing secondary to perceived drop in BP leads to decreased parasympathetic and increased sympathetic outflow to the heart, leading to increased HR, contractility, SV, and vasoconstriction of arterioles and veins

Sulfonylureas

Sulfonylureas: Commonly used medications include Glyburide, glipizide, and tolbutamide. Mechanism: ↑ Insulin secretion by closure of ATP-gated K channel in pancreatic β cell membrane. Remember that the GLUT2 transporters bring glucose into beta cells where it is metabolized to produce ATP via aerobic respiration. The rise in ATP is the trigger for the beta cell to release insulin. When the K channel closes, the cell is depolarized (because it's an inward rectifying channel) causing voltage-gated Ca2 channels to open, which triggers the release of insulin. Special notes: Glyburide dose must be decreased with renal failure. Glipizide must be reduced with hepatic failure. Also, care must be taken to prevent overadministration and subsequent hypoglycemia.

surfactant composition

Surfactant consists primarily of lecithin, aka phosphatidylcholine or phosphatidylglycerol. A *lecithin:sphingomyelin ratio of >2.0* in the amniotic fluid indicates fetal lung maturity. If the ratio is less than 2:1, prophylactically treat mother with glucocorticoids. stimulated by cortisol/CRF, also insulin and thyroxine

Secondary amyloidosis

Systemis deposition of AA amyloid derived from SAA, an acute phase reactant, which is increased in chronic inflammatory states (autoimmune diseases, lupus, RA, Crohns, UC, chronic osteo myelitis) Also happens in malignancy, which leads to a chronic inflammatory state.... as well as Familial Mediterranean Fever. Association between secondary amyloidosis and neoplasm: Hodgkin's disease (4% of patients), hypernephroma (3% of patients)

TBG

TBG (thyroxine-binding globulin) binds most T3 or T4 in peripheral blood • Only free T3 or T4 is active. TBG bound T3 or T4 is inactive. • Conditions where TBG is increased or decreased can affect total T3 or T4 levels. For example, increased estrogen during pregnancy causes increased TBG, which results in increased total T3 and T4 levels. However, the free T3 and free T4 levels are actually normal (therefore, pregnancy is not a hyperthyroid state).

p53

TP53 gene on chromosome 17p --> p53 P53 is a *tumor supressor* gene which is like a 'traffic cop'... before cell goes G1->S, it has to pass p53. A NORMAL, non mutated p53 can either: 1) ARREST- In presence of DNA damage, p53 binds DNA, and activates expression of several genes, including *p21* and other *CDK inhibitors*. If CDK inhibitors such as p21 are activated, they bind and compete with cyclin dependent kinases (CDKs), this means the *Cyclin D1-CDK complex* does NOT form, and the cell is *arrested*. (see below on Rb for more) 2) REPAIR- p53 induces a *DNA polymerase* to *repair* slightly damaged DNA. 3) APOPTOSIS. If the cell is *too damaged* p53 calls in an *apoptosis regulator known as *BAX* .Bax works by blocking * Bcl-2.* Bcl-2 stabilizes the mitochodrial membrane by preventing cytochrome C from leaking from mitrochondria into cytoplasm. Thus, p53 calls in BAX, so BCl-2 cannot do its job.... ultimately allowing leakage of cytochrome C, which tiggers *caspases* to induce apoptosis*. HOWEVER, if P53 is mutated, we do NOT get p21, thus the damaged cell is NOT *arrested*.... we do NOT get DNA polymerase so the cell is NOT *repaired*.... and we do NOT get BAX, so the cell is NOT *apoptosed*... thus it keeps going through the checkpoint. note, BOTH copies of p53 must be knocked out for tumor formation.

Hemoglobin structure

Tetramer (4 subunits); each subunit polypeptide has a heme molecule at its center and each heme molecule can carry 1 oxygen molecule Hemoglobin A (adult): α2β2 Hemoglobin A2 (adult): α2δ2 (2 alpha 2 delta) Hemoglobin F (fetal): α2γ2 - elevated in sickle-cell disease patients

Huntington's disease

The gene for Huntington's disease is located on chromosome 4 The cause of the disease is an abnormally long, tandemly repeated trinucleotide (CAG) The abnormal gene, called HD, encodes for a protein, called huntingtin which is expressed in many tissues; its function is currently unknown. Protein accumulates inside neuronal nuclei, forming inclusions as well as accumulating inside some nerve cell processes. Decreases GABA in striatum, which *disinhibits* the thalamus, so the thalamus can *excite* the *premotor cortex* This favors the *direct pathway* Characterized by: Choreiform movements May later develop parkinsonism with bradykinesia and rigidity Forgetfulness and thought and affective disorders Psychotic behavior/ Dementia

corona radiata

The group of granulosa cells surrounding the oocyte is then called Corona Radiata.

After growth plate forms

The growth in length of long bones involves the following two major events: (1) interstitial growth of cartilage on the epiphyseal side of the epiphyseal plate (2) replacement of cartilage on the diaphyseal side of the epiphyseal plate with bone by endochondral ossification. The epiphyseal (growth) plate is a layer of hyaline cartilage in the metaphysis of a growing bone that consists of four zones. 1. Zone of resting cartilage. 2. Zone of proliferating cartilage. 3. Zone of hypertrophic cartilage 4. Zone of calcified cartilage.

Celiac morphology

The histopathologic picture is characterized by - increased numbers of intraepithelial CD8+ T lymphocytes - with intraepithelial lymphocytosis - crypt hyperplasia - villous atrophy Damage MOSTLY in duodenum (!!!!), vs jejenum and ileum

Insulin action

The insulin receptor is a tetrameric RTK (receptor tyrosine kinase) consisting of two α and two β subunits. It is found on the target tissues of insulin and initiates an intracellular phosphorylation cascade when it binds insulin. The major targets of insulin are the liver, adipose tissue and skeletal muscle. Insulin increases glucose uptake on its target cells by up-regulating the number of GLUT-4 receptors on their plasma membranes. Insulin responsive cells (adipocytes and skeletal myocytes) express GLUT-4 (ie, GLUT-4 is insulin dependent).

Diabetic ulcers

The most common foot injuries leading to lower extremity amputation Risk factors for amputation of the diabetic foot include: Peripheral neuropathy Structural foot deformity Ulceration, infection and peripheral vascular disease The arterial occlusion typically involves the tibial and peroneal arteries but spares the dorsalis pedis artery. Smoking, hypertension and hyperlipidemia contribute to the increased prevalence of peripheral arterial occlusive disease in diabetics

Cryptorchidism

The most common genital problem encountered in pediatrics. Generally refers to an undescended or maldescended testis.

Colorectal cancer metastasis

The most common site of metastasis is the liver. Colorectal carcinomas are the most common cancer to metastasize to the liver, largely due to the rich portal circulation. In fact, in the US, liver cancer secondary to colorectal carcinoma metastasis is far more common than a primary hepatocellular carcinoma. . The second most common location is the lungs. Finally, peritoneal seeding may lead to ovarian involvement.

Mucosa

The mucosa, or inner lining of the GI tract, is a mucous membrane. It is composed of : (A) a layer of epithelium in direct contact with the contents of the GI tract (B) a layer of connective tissue called the lamina propria (C) a thin layer of smooth muscle (muscularis mucosae).

osteoblast vs osteoclast hematopoiesis

The osteoclast is derived from a monocyte precursor cell located in the hematopoietic marrow. This is in contrast to osteoblasts, which are of mesenchymal derivation.

Zone 1 liver

The periportal zone I is nearest to the entering vascular supply and receives the most oxygenated blood. Zone I hepatocytes are specialized for oxidative liver functions such as gluconeogenesis, β-oxidation of fatty acids and cholesterol synthesis. affected by viral hepatitis, eclampsia.

Barrett's esophagus

The stomach is lined by columnar epithelium, which the esophagus is lined with squamous epithelium. Chronic acid reflux (GERD) causes damage of squamous epithelium of distal esophagus. There is healing and re-epithelialization in abnormally low pH environment, causes a *metaplasia* of the squamous cells of esophagus to transform into a more acid-resistant *non-cilliated columnar epithelium w/ goblet cells* - presence of goblet cells in the esophagus defines the term intestinal metaplasia.

3 organs most affected by CF

The sweat gland Which produces excessively salty sweat The lung In which COPD invariably develops and is usually the cause of mortality The pancreas Which fails to produce adequate bicarbonate ion and water, and produces inadequate digestive enzymes - pancreatic insufficiency.

ALL symptoms

The symptoms of ALL are indicative of a reduced production of functional blood cells, due to the fact that the leukemia wastes the resources of the bone marrow, which are normally used to produce new, functioning blood cells. These symptoms can include: - fever - increased risk of infection (especially bacterial infections like pneumonia, due to neutropenia; symptoms of such an infection include shortness of breath, chest pain, cough, vomiting, changes in bowel or bladder habits), - increased tendency to bleed (due to thrombocytopenia) - signs indicative of anemia including pallor, tachycardia (high heart rate), fatigue and headache.

4 layers GI tract

The wall of the GI tract from the lower esophagus to the anal canal has the same basic, four-layered arrangement of tissues. The four layers of the tract, deep to superficial 1) mucosa 2) submucosa 3) muscularis 4) serosa/adventitis

theca interna vs externa

Theca interna (steroid producing - androstenedione) Theca externa (organized fibroblasts - aids in rupture of the mature oocyte)

Type 2 diabetes meds

There are 5 major oral antidiabetic agents, which can be remembered with the mnemonic STαB Mellitus: Sulfonylureas Thiazolidinediones α-glucosidase inhibitors Biguanides (metformin) Meglitinides.

Left congestive heart failure

There are two categories of left heart failure: 1) *Systolic dysfunction* is due to *decreased ventricular contraction* Causes include: - Ischemia - HTN (concentric LV hypertrophy leads to ischemia) - myocarditis - dilated cardiomyopathy - restrictive cardiomyopathy (can't fill the heart) - fluid overload. 2) Diastolic dysfunction is due to a noncompliant ventricle

Types of burns

Thermal (flame, scald) Chemical (acid) Radiation (UV) electrical (current trough body)

Functions of skin and in burns

Theromoregulation- so with burns they lose a lot of heat, must keep warm fluid control- loss of water and proteins mechanical barrier, high risk of infection - use antibiotic ointment and tetanus prophylaxis if necessary

Betz cells

They are pyramidal cell neurons located within the fifth layer of the grey matter in the primary motor cortex. Betz cells represent about 10% of the total pyramidal cell population of the human primary motor cortex

AIDS

They must be HIV positive, and exhibit either CD4 count under 200, or the presence of one or more opportunistic infections.

Atherosclerosis

Thickening/plaque (mostly cholesterol) of the *INTIMA* which affects blood flow.... primarily large and medium-sized *muscular* arteries are the primary sites of atherosclerosis.

acute inflammation events

Three main processes occur: 1) Vasodilation Accounts for warmth and redness Increases blood flow ( ↑hydrostatic pressure) (vascular permeability still not increased yet) 2) Increased permeability Allowing fluid and blood proteins to move into the interstitial spaces (↓ plasma osmotic pressure) Oedema may occur within a few minutes 3) Stasis Due to concentration of rbc's as a result of fluid loss ↑ Blood viscosity Migration of WBC (neutrophils and perhaps a few macrophages) out of venules and into interstitial spaces

Diagnose Rheumatic fever

To diagnose Rheumatic fever you must have: - evidence of recent Strep infection (eg, serology (ASO titer or anti-DNase B titer), and either: ≥ 2 major Jones criteria - or - 1 major Jones criterion and 2+ minor Jones criteria

Koch's postulates

To establish that a specific pathogen is the cause of the disease, the researcher must: o Find the same pathogen in each individual investigated o Isolate the pathogen from the diseased subject and grow the microbe in a pure culture o Induce the disease in experimental animals by transferring the pathogen form the culture o Isolate the same pathogen from the experimental animals after the disease develops.

mechanical back pain

Trauma, lumbar disc prolapse or spondylosis. spondylolisthesis... spinal stenosis,

treat hypertension

Treatment strategy is aimed at reducing controllable risks such as limiting salt intake, losing weight, avoiding alcohol and smoking, and increasing exercise. while using pharmaceuticals. Antihypertensive medication, should be started for persistent blood pressure greater than >140/90. Two drugs in combination can be considered for bps 160/100. - Diutetics - Sympatholytics - Vasodilators - Angiotensis agents

Triple therapy

Triple therapy is used in regions with low resistance rates. It includes a proton pump inhibitor (PPI), clarithromycin and amoxicillin.

causes of infarcts

Tromboembolism Vasospasm Expansion of an atheroma due to hemorrhage within a plaque Extrinsic compression of a vessel (e.g., by tumor).

Systemic TB infection

Tuberculosis can infect the kidneys, resulting in malaise, dysuria, gross hematuria, and sterile pyuria. Skeletal infection most commonly involves spine, leading to destruction of intervertebral discs and vertebral bodies. This is called Pott's disease. CNS infiltration of Mycobacterium tuberculosis can cause meningitis and formation of granulomas in brain. Joint infection in tuberculosis causes chronic arthritis. Miliary tuberculosis (aka "disseminated tuberculosis") is a form of tuberculosis that is characterized by a wide dissemination into the human body and by the tiny size of the lesions.

primary TB

Tuberculosis starts as a tiny focus of infection in peripheral lung (the Ghon focus), usually in lower segment of upper lobe or upper segment of lower lobe (note, some sources do middle lobe). Macrophages try to digest TB but cannot fully, so TB is carried in macrophages to the hilar lymph nodes, which enlarge as the immunological reaction drives the generation of granulomatous inflammation, as immune cells (macrophages and T Helper lymphocytes) wall off the infection into a granuloma, forming a latent infection. Tuberculosis gets its name from the small granulomas called tubercles, consisting of epitheliod cells, giant cells, and lymphocytes, where the bacteria are contained.

Tunica intima

Tunica intima: Innermost layer consisting of a single layer of squamous endothelial cells and loose subendothelial connective tissue. Most arteries also contain an internal elastic lamina *between* the *intimal and medial layers*. Structures of the intima are *longitudinally* oriented.

Tunica media

Tunica media: Middle layer consisting of smooth m., elastic sheets and reticular (type III collagen) fibers Muscular arteries have an *external elastic lamina* between the *medial and adventitial layers*. Structures of the media are *circumferentially* oriented.

Volvulus

Twisting of bowel along its mesentary, resulting in obstruction and distribution of blood supply. Usually happens in *sigmoid colon* (elderly) and *cecum* young)

Two major theories for the developmentof endometriosis :

Two major theories for the development of endometriosis : 1) The metastatic theory due to Retrograde menstruation 2) The metaplastic theory. The Endometrium could arise directly from coelomic epithelium (mesothelium of pelvis or abdomen)

Glomerulonephritis

Type 3 HS. antigen-antibody complexes deposit on the renal glomerular basement membrane → inflammatory response • Most commonly implicated antigens: DNA, insulin, thyroglobulin, group A streptococci, and foreign serum • Diagnosis: complexes detected using fluorescent antibody against the antigen, antibody, or complement. A "lumpy-bumpy" pattern of fluorescence results from the random deposition of the complexes.

Type 4 hypersensitivity

Type IV Hypersensitivity: Cell-mediated or delayed type response, sometimes referred to as delayed type hypersensitivity (DTH). Initiated by antigen-activated T cells (including both CD4 and CD8 cells) • Cytotoxic T cells, monocytes, and macrophages cause direct tissue damage ie: IDDM MS celiac RA There is a component of antigen/antibody complex deposition involved in RA (thus some sources consider it to also be Type III Hypersensitivity), however RA is generally classified as Type IV Hypersensitivity because of the T-cell mediated inflammation. Rheumatoid factor (IgM) can react with the Fc domain of IgG molecules → IgM-IgG complexes that deposit in synovial tissue. This causes initiation of the complement cascade and release of cytokines which activate cell mediated immunity and T-cell mediated damage to bone, cartilage and the synovium

GI Ulcers vs erosion

Ulcers (GI): breach in the epithelium of the mucosa AND muscularis mucosae INTO the submucosa or deeper Erosion (GI): breach in the epithelium of the mucosa ONLY

disk blood supply

Up until the age of eight years, there are small blood vessels supplying the more centralized disc material which help heal it when it is injured. As a body ages, the liquid center of the nucleus pulposus becomes solidified the cartilage component loses water and actually forms a solid disc-shaped structure. So the blood supply is relegated only to the outer most ligamentous structures The rest of the disc must obtain sustenance from the diffusion of tissue fluid across the cartilaginous end plates.

B-blocker uses

Used to treat *hypertension*; used to treat *heart failure* because sympathetic activity on the heart also causes maladaptive remodeling of the failed heart, (similar to angiotensin II) -used to treat *coronary artery disease* because beta blockade will prevent sympathetic stimulation of the heart, which would increase myocardial oxygen demand.

Cleft Lip and Palate

Usually occur together: Cleft lip and palate are associated with the teratogens *phenytoin* and *retinoic acid*. Cleft lip and palate are among the common congenital abnormalities in *Trisomy 13*.

dementia brain morphology

Variable degree of cortical atrophy Widening of the cerebral sulci compensatory ventricular enlargement

Vitamin K deficiency

Vitamin K is activated by *Epoxide Reductase* in the liver*, which is necessary for gamma carboxylation of factors 10, 9, 7, 2. Both PT and PTT are ↑ in deficiency. Deficiency occurs in: 1) Newborns - breast milk is vit K deficient and GI tract isn't colonized yet with vit K-producing bacteria → hemorrhagic disease of the newborn (!!).... Note, we give ALL newborns vitamin K to avoid this!!! 2) Long term antibiotic therapy- (kills gut flora) 3) Malabsorption (K is fat soluble). 4) Cirrhosis - decreased coagulation factors - decreased activation of vitamin K

Residual volume

Volume in lungs which *cannot be exhaled*

why must we use heparin bridge for warfarin

Warfarin inhibits epoxide reductase in liver, so we do not activate Vitamin K, and we don't get synthesis of factors 2, 7, 9, 10 as well as Protein C and Protein S. Protein C and Protein S have shortest half lives, so they degrade BEFORE factors 2, 7, 9, 10. Thus, without Proteins C and S, factors V and VIII are amplified, and factors 2, 7, 9, 10 are still high... so we get risk of thrombosis. Heparin bridge avoids this risk and prevents skin necrosis.

Findings in acute tubular necrosis

We have *decreased tubular function* so there is *decreased resorption of BUN*, and a *BUN:Creatinine < 15* Decreased resorption of sodium, so *FENa > 2%* Inability to concentrate urine *urine osm < 500*

gliadin is found in

Wheat Oat Barley Rye

TE fistula presentation

When baby consumes food, it gets stuck in *atresia pouch of the proximal esophagus*, so there is difficult feeding, and *vomiting*. Also, there is *polyhydramnios* → excess amniotic can be detected prenatally → amniotic fluid is not *recycled as efficiently* but is still produced by fetal kidney, so levels are *high* [Note: contrast this to oligohydramnios in autosomal recessive polycystic kidney disease → ↓ of renal function → ↓ amnionic fluid production (recycling but not producing)

changes in first breath

When the baby draws its first breath, the alveoli in the lungs open and fill with air, reducing the pressure in the pulmonary tissue. Blood from the right ventricle flows more quickly into the lungs, decreasing the pressure in the right atrium. The pressure in the aorta increases and becomes greater than the pressure in the pulmonary arteries, *preventing* blood from entering the aorta through the ductus arteriosus. The ductus arteriosus begins to contract. After a few days, the ductus arteriosus, closes off completely The greater amount of blood flowing into the lungs returns to the heart via the pulmonary veins and enters the left atrium, causing increased pressure in the left atrium. The pressure is now higher in the left atrium than in the right atrium, closing the foramen ovale. With the foramen ovale closed off, all the blood entering the right atrium must enter the right ventricle and be pumped into the pulmonary arteries.

Explain the mechanisms by which cardiac failure causes shortness of breath.

When the left side of the heart fails, blood back logs all the way back into the lungs .This raises hydrostatic pressure (forces out) in the pulmonary venules and veins, a leakage of fluid, and pulmonary oedema. This will cause shortness of breath as the fluid will disrupt the diffusion of oxygen from the lungs into the blood, causing increasing respiratory rate to increase. Neural input from J receptors gives rise to sensations of pressure in the chest and

Congestion phase

When you get an infection you congest blood vessels by dilating them, increasing amount of blood in them, and in edema.

A2 agonist sides

Without sympathetic stimulation, as expected, side effects include: - bradycardia - dry mouth (xerostomia) - sedation. Because it downregulates the sympathetic nervous system, abrupt cessation of α2 blockers can cause a sympathetic surge and resulting hypertension.

Genital development

Y chromosome has SRY gene. SRY-gene codes for Testes Determining Factor Its expression causes the development of primary sex cords, which later develop into seminiferous tubules. These cords form in the central part of the yet-undifferentiated gonad, turning it into a testis. The now induced Leydig cells of the testis then start secreting testosterone while the Sertoli cells produce anti-Müllerian hormone. • Mullerian inhibitory hormone (MIH) - which induces regression of the Mullerian duct. • A steroid hormone - testosterone - which stimulates development of the Wolffian tract.

Zollinger Ellison syndrome

ZES is caused by gastrin-secreting tumors (gastrinoma) that are most commonly found in the pancreas or the small intestine near pancreas (eg, duodenum). This excess gastrin leads to excess production of HCl → treatment resistant (!!) peptic ulcers, duodenal ulcers, maybe jejunum ulcers, chronic watery diarrhea, steatorrhea, vomiting. Gastrin activates stomach parietal cells, and also and enterochromaffin-like cells (secrete histamine) Association with MEN I

Liver zones

Zone 1(periportal), zone II (transition zone) zone III (centrilobular)

local response to burns

Zones of thermal injury explain the relationship of depth and extent of injury. 1. Zone of hyperemia: Outermost area of minimal injury, similar to a superficial burn and heals rapidly, there is no cell death. Tissue is red but blanches. 2. Zone of coagulation: Greatest area of tissue necrosis and is at the core of the wound. Protein coagulation and cell death has occurred. Tissue is expected to be black, gray, or khaki to white and does not blanch with pressure. 3. Zone of stasis: Area directly next to the zone of coagulation with vascular damage (reduced blood flow) and potentially reversible injury. Tissue is red but does not blanch with pressure. The local response to burn injury leads to coagulation of cellular proteins, production of complement, production of histamine, and production of oxygen free radicals. Activation of the complement system and histamine leads to increased vascular permeability. Oxygen free radicals create tissue injury and the formation of edema. Consequences of edema include pulmonary vascular injury, pulmonary interstitial edema, intra-alveolar hemorrhage, red blood cell destruction and intravascular hemolysis. Total cell destruction may occur due to alterations in the structure of DNA

extrinsic muscles of the tongue

a set of four skeletal muscles that originate outside of the tongue and attach to it. They function to move the tongue and include the: genioglossus hyoglossus styloglossus palatoglossus. All innervated by CNXII EXCEPT palatoglossus (CNX)

hepatocellular carcinoma morphology

a) Pleomorphism (variation in size and shape) b)Abnormal nuclear morphology c)Mitoses d)Loss of polarity

Acute kidney injury/ renal failure

abrupt, severe decrease in renal function characterized by *azotemia* which means increase in nitrogenous waste products in the blood (BUN or ↑ in serum creatinine ).... OR patients can have oliguria (an abrupt ↓ in urine output) Therefore, AKI can be: - Oliguric (urine output <400mL/day); or - Non-oliguric (urine output ≥ 400mL/day)—please remember that AKI is *not always* accompanied by oliguria! Can be: - Prerenal injury/azotemia - postrenal injury/azotemia - intrarenal azotemia

l4-l5 herniation

affects L5 nerve root/dermatome... lateral leg, big toe, dorsal foot. weak dorsiflexion (cannot stand on heels)

c5-c6 herniation

affects c6 nerve root and dermatome..... lateral surface of forearm, thumb, pointer finger affects biceps, brachialis, brachioradialis, so weak flexion of forearm, supination. Afffects musculocutaneous nerve, decreased bicep and brachioradialis reflex jerk

c6-c7 herniation

affects c7 nerve root and dermatome. (middle finger) Weakened triceps, wrist extensors

L5-s1 herniation

affects gactroc, soleus, cannot plantar flex (stand on toes).... decreased ankle jerk

brain injury

after traumatic brain injury, the brain is bathed with potentially toxic neurochemicals. • Catecholamine surges in the plasma (higher catecholamine levels correlated with worse clinical outcomes) and in the (CSF) of patients with head injuries. • Head injury causes release of free radicals and breakdown of membrane lipids. These lipids fragment into mediators of inflammation. • The excitotoxic amino acids (ie, glutamate, aspartate) initiate a cascade of processes culminating in an increase in intraneuronal calcium and cell death.

factors affecting wound healing

age nutritional status stress co-morbidities drugs (ie, aspirin reduces)

tidal volume

air moved in/out of lungs with quiet breathing

Somatostatin

aka (GH inhibitory hormone), it is secreted by both *delta aka D cells*of the pancreatic islets AND intestinal mucosa. Stimulated in response to excessivey high H+ in the GI lumen. In turn, it inhibits GI hormones such as gastrin and secretin. It also inhibts both insulin AND glucagon.

Hirschsprung's disease and GI plexus

aka Aganglionic megacolon: results from failure of *neural crest cells* to form the *ganglionic plexus'* in the *sigmoid colon and rectum*. It is associated with loss of peristalsis resulting in fecal retention, chronic constipation and abdominal distension. Normally, the bowel wall has Mucosa, submucosa, Muscularis propria, Serosa. Muscularis propria has inner circular layer, outer longitudinal layer. In between then is the *Auerbach/myenteric plexus* which is "essential* for peristalsis and relaxation. Second set of ganglionic cells is called *Meissner's plexus* and it is in the *submucosa*. Helps to regulate *blood flow, secretion, etc* In *Herschsprung's*, you lack *both ganglion* in *rectum* and MAYBE *sigmoid colon*.

low molecular weight heparin

aka Enoxaparin Same mechanism, but preferentially inhibits Xa. This prevents cleavage of prothrombin--> thrombin. Mnemonic: think "EnoXaparin → Xa" Better bioavailability and longer half-life LMWH is given subcutaneously. It is used in DVT prophylaxis and in treatment of established venous thrombosis while bridging with

complement c1 inhibitor deficiency

aka hereditary angioedema. C1 inhibitor controls c1, makes it act when necessary. deficiency of it leads to overactivation of complement.

Aortic regurgitation murmur

an *early diastolic*, "blowing" decrescendo murmur best heard in the *third left intercostal space* and radiating along the sternal border. It is also associated with the *Austin Flint murmur*, a *separate* low-pitched rumble heard at the apex in late diastole.

Thyroxine binding globulin

binds most T3 or T4 in peripheral blood Only free T3 or T4 is active. TBG bound T3 or T4 is inactive. Conditions where TBG is increased or decreased can affect total T3 or T4 levels. For example, increased estrogen during pregnancy causes increased TBG, which results in increased total T3 and T4 levels. However, the free T3 and free T4 levels are actually normal (therefore, pregnancy is not a hyperthyroid state).

Stable angina presentation

chest pain (lasts less than 20 minutes) that radiates to left arm or jaw. - diaphoresis (sweating) - SOB

treat dementia

cholinesterase inhibitors SSRI's for depression -

SLE overview

chronic, autoimmune inflammatory disorder that affects multiple body systems, mostly in child bearing females, also in blacks, hispanics, asians. (note, female bias is less profound in children and adults, this makes sense, because children and old adults have less estrogen) Flares and remissions are common. Antigen-antibody complexes are deposited in multiple tissues, and this activates complement, which damages those tissues. (Type 3 HSR) S/Sx: joint/muscle/chest pain, teadaches, fever, oral ulcers, rashes, damages serosa. Destruction of cells in the blood, so antibodies against: (this is Type 2 HSR!!!) - RBCs lead to anemia, - against platelets thryombocytopenia, - against WBCs leads to leukopenia. Common death causes are renal failure and infection (antibodies destroy WBCs). 30% of patients get antiphospholipid syndrome (anti cardiolipin, lupus anticoagulant. Latter makes patient HYPER coaguable, produce thrombosis in both arteries (stroke) and veins (DVT, Budd Chiari in hepatic vein), Infertility, pregnancy loss

chymotrypsin

cleaves peptide amide bonds where the carboxyl side of the amide bond is a large hydrophobic amino acid (tyrosine, tryptophan, and phenylalanine)

Secretin

comes from duodeal S cells. The stimuli for is is H+ and FA's in duodenum. causes epithelial duct centrioacinar cells to secrete fluid rich in bicarb.

common complications of myeloproliferative disorder

common complications: - hyperuricemia and gout (when you produce many RBC's, nucleus has to be removed via purine degradation pathway, and end result is uric acid) - progression to marrow fibrosis - transformation to acute leukemia (mutations in a stem cell progress)

metabolic acidosis response

compensatiory respiratory response, increase ventilation, decreasing PCO2, raising pH close to normal. This is the short term response, begins 30 minutes, complete by 12-24 hours. Renal response of enhanced acid excretion as NH4+, and increased production and release of HCO3-

avascular necrosis of bone

composed by 2 phases : Cell Necrosis Healing response Initial inflammatory response (initial step of repair, removal, and reconstruction of the infarcted area). Bone infarcts are composed of 4 zones A central zone of cell death Zones of ischemia, Hyperemia, and Normal tissue

Adrenal medulla

composed of chromaffin cells derived from neural crest

Lumbar spinal stenosis

congenital narrowing of spinal canal combined with degenerative changes (herniated disc, hypertrophy of facet joints and ligmentum flavum) -gradually progressive back.leg pain standing/walking that is relieved by sitting/lying down (Iimproved by delordosing, worsened by lordosing) - neurogenic claudication Gold standard is CT myelogram Treat with physio, NSAIDS, operative decompression if not improved

Signs of anaphylaxis

congesion, dizziness, rash, hoarseness. increased respiration. tachycardia, hypotension. nausea, vomiting.

Rickets

defective mineralization with low vitamin D in children. -Pigeon breast deformity (anterior protrusion of the sternum) - frontal bossing (prominent forehead) - rachitic rosary (bony prominence at costochondral junctions) - bowing legs (Genu varum, weakened long bones) Osteoid is deposited in places

Chronic bronchitis definition

defined clinically as a *productive cough* for *at least 3 months* in *2 consecutive years*. (patients say they cough up cups/buckets of mucus, so much!)

GERD

definition of (GERD): symptoms OR mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. due to due to LES incompetence, transient *LES relaxation*, or a hiatal/diaphragmatic hernia.

emission vs ejaculation

emission- phase when sperm moves from testes up to prostatic urethra. This phase is under control of sympathetic nervous system. The hypogastric nerve Ejaculation- phase when sperm moves from prostatic urethra to the outside This phase is under control of visceral and somatic nerves. The pudendal nerve

hemolytic disease of newborn overview

emolytic disease of the newborn (erythroblastosis fetalis): transplacental transfer of maternal anti-Rh IgG binds to Rh+ fetal RBCs → fetal RBCs are destroyed (relative hypoxia, altered cellular metabolism) Prevention of erythroblastosis fetalis is required when the mother is Rh- and her fetus is Rh+: administer anti-Rh antibody (RhoGAM) to the mother at 28 weeks gestation and again within 1-2 days of delivery to neutralize fetal Rh antigens that enter the mother's circulation during placental delivery → this prevents stimulation of the maternal immune system and injury to future Rh newborns

Adenomyosis

endometrial glands and stromal implants are found in the myometrium This condition leads to uterine enlargement and irregular bleeding

Achalasia

failure of LES relaxation + loss of distal esophageal peristalsis. Failure of complete *LES relaxation* is *damage to inhibitory (NO synthase producing) neurons that enable relaxation Degeneration of neurons in esophageal wall (*Auerbach's / myenteric plexus*) → loss of smooth muscle contraction/motility → uncoordinated, or lack of, peristalsis Lack of peristalsis causes *progressive dysphagia* to *BOTH solids and liquids*, (peristalsis is necessary to move both solids and liquids)..... this leads to nocturnal regurgitation of undigested food.... and also *massive dilation of esophageal wall* Also increased risk for *esophageal* squamous cell carcinoma

SLE clinical features

fever, weight loss, fatigue - Lymphadenopathy - Raynaud phenomenon (arterial vasospasm of artery and turns it white.... over time with ischemia it turns blue... then when vasospasm releases it turns red) - Malar 'butterfly' rash, especially on on exposed to sunlight - discoid rash (circular, erythematous with scaling and it scars)

Nitrates overview

first-line drugs in angina. Their main effect is to cause peripheral vasodilatation, especially in the veins. The pooling of blood in (veins) reduces venous return, and the end-diastolic ventricular volume is decreased. Reduction in the distension of the heart wall decreases oxygen demand and the pain is quickly relieved. GTN given sublingually to avoid first-pass metabolism is used to treat acute anginal attacks. e.g., nitroprusside, nitroglycerin, isosorbide dinitrate Nnitrates have greater effect on *veins* and therefore cause *decreased preload* by *reducing venous return*, more so than reducing *afterload*. This reduced preload causes *decreased myocardial oxygen consumption*, increases coronary blood flow, improving ischemia. - decreases LVEDV/LVEDP At *higher doses*, nitrates also act on *arterioles* as well and reduce *afterload*. NO is normally produced by the endothelial cells of the blood vessel, but the action of NO is on the smooth muscle cells.

thickening of commissures murmur

generate a complex murmur with components of both aortic stenosis (AS) and aortic insufficiency (AI).

how to differentiate ACTH secreting pituitary adenoma from paraneoplastic ACTH secretion

high dose dexamethasone- a cortisol analogue, that will suppress ACTH. If the patient has suppressed cortisol levels in response to low-dose dexamethasone → the patient may look like they have Cushing syndrome, but their ACTH-cortisol axis is probably normal. If the patient has persistently elevated cortisol in response to low-dose dexamethasone, but their cortisol levels are reduced in response to high-dose dexamethasone → likely an ACTH-secreting pituitary adenoma (Cushing disease) If the patient fails to suppress cortisol in response to either low-dose or high-dose dexamethasone → Cushing syndrome, either due to: - Cortisol-producing tumor in the adrenal cortex (high serum cortisol, low serum ACTH) or - Ectopic ACTH-secreting tumor (high serum cortisol, high serum ACTH), most commonly caused by small cell carcinoma of the lung. The ectopic ACTH-secreting tumor will have much higher ACTH levels than the tumor in the adrenal cortex.

Pulmonary hypertension

high pressure in pulmonary circuit... Normal pulmonary artery pressure = *10-15* mmHg

Chronic bronchitis is associated with:

highly associated with *smoking*. Respiratory epithelium is *normally* classified as *pseudostratified ciliated, columnar epithelium* that sit on a basement membrane. Underneath that is *lamina propria* which contains *venules* which bring warm blood to region to warm it. Underneath *lamina propria* is *submucosa* which contains glands: 1) serous and 2) mucinous Serous gland produces watery fluid to go up above basement membrane to epithelium and humidify air. Mucinous glands produce mucus to line epithelial surface and trap bacteria, etc. Most are multicellular, but *goblet cells* are *single-celled* glands. In smokers, they bring in a *ton of pollutants* so the lung increases amount of mucus to deal with them, so you get *hypertrophy* of the *mucinous* glands. The *Reid Index* measures the ratio of *gland thickness* to wall thickness, so in COPD this goes up!! (normal <40%, here maybe 50%+) most mucus is coughed up, but some goes back, and plugs airway which causes trapping and *obstruction* of getting air out. There is also a *metaplasia* of *pseudostratified cilliated columnar epithelium* to *squamous cells*.

hCG and thyroid

hormone hCG is structurally similar to TSH and has some weak thyrotropic activity, which is estimated at approximately 0.025% that of TSH - some sources suggest that hCG and the TSH receptor share a common subunit

Denosumab

human monoclonal antibody for the treatment of osteoporosis. Denosumab is designed to inhibit RANKL (RANK ligand), a protein that acts as the primary signal for bone removal.

Graves disease presentation

hyperthyroidism - diffuse bilateral uniform goiter (hyperplasia/hypertrophy of thyroid) - exopthalamos and pretibial myxedema (NOT due to hyperthyroidism... due to fibroblasts behind the orbit and overlying tibia having TSH receptors.... in response to antibody, they secrete excess GLYCOSAMINOGLYCANS (chondroitin sulfate and hyaluronic acid) which build up.

large arteries

ie, aorta, common carotid Rich in elastic fibers. Elastic arteries are CONDUCTING vessels. These large arteries exit from the heart and and have a prominent tunica media (!!!) In large arteries., the tunica adventitia contains the vasa vasorum. Structures of the adventitia are longitudinally oriented.

Adenoma-carcinoma sequence

if patient develops mutation in *APC tumor suppressor gene* (adenomatous polyposis coli) this creates risk for *development of a polyp*. Next, a *K-RAS mutation* allows *formation* of polyp, and if we get *p53 mutation* (along with *high COX expression*) we get progression to adenocarcioma from the polyp. Note: ASPIRIN likely protects against this by inhibitng COX (!) See above notes for p53 and Rb!!

Renal artery stenosis

if you have stenosis of renal artery, there is *less blood flow to the glomerulus*.... so the JGA responds by secreting Renin, etc etc... AT2 formed which: 1) Powerful vasoconstrictor- *Directly contracts arterolar smooth muscle* to *increase peripheral resistance*. 2) promotes adrenal release of aldosterone, which grabs sodium from DCT to expand plasma volume.

Type III Hypersensitivity:

immune complex reactions Circulating antigen-antibody complexes deposit on the surface of blood vessels activating complement that eventually leads to tissue destruction. (If the complexes are formed extravascularly, they are called in situ immune complexes). ie, SLE

B-cell survival

in bone marrow, if immature B-cell (that express surface IgM and IgD) recognizes self MHC molecules or other self-antigens it is DELETED. If it does NOT, it undergoes NEGATIVE selection, and becomes mature B-Cell. Then, if it gets costimulation (CD40L on helper T-cell binds to CD40 on B-cell). it activates, prolifferates, and differentiates into clone of plasma cells. - Helper T-cell then secretes IL-4, mediates B-Cell isotype switching, hypermutation, mature to plasma cells, If it does NOT get co-stimulation, it undergoes anergy in secondary lymphatic tissues/blood Other way to activate mature B cell is: 1) antigen binds IgM or IgD , causes sell to become plasma cell and secrete IgM

grey v white matter in brain and spine

in spine, grey inside, white outside.... (brain reverse)

malaria life cycle stages

liver stage blood stage sexual stage

chief cells

located mostly in fundus, secrete pepsinogen, small amounts of gastric lipase.

characteristics of transformed malignant cells

loss of contact inhibition able to bind laminin and fibronectin in connective tissues secrete collagenases and proteases able to keep dividing

Hypo-osmotic dehydration

loss of hypertonic fliud from ECF (ie Addison's, lack of aldosterone, adrenal insufficiency) ECF volume decreases, and ECF osmolarity decreases. So, there is a fluid shift from ECF to ICF to balance the osmolarity ICF volume will increase ICF osmolarity will decrease

risk factors for falls

loss of vision postural hypotension decreased muscle strength Epilepsy demyelinating disease parkinsons visual problems Alcohol drugs medication environment

causes of sickling

low O2 - Painful crises during dehydration, infection, acidosis, temperature extremes, or sudden decreases in ambient O2 tension (e.g. high altitude)

Hypoxia

low oxygen delivery to tissue. Caused by: - Ischemia - Hypoxemia - decreased O2 carrying capacity of blood

findings of folate/B12 deficiency

megaloblastic anemia - hypersegmented neutrophils (normally, neutrophils have 3-5 lobes, >5 is hypersegmented) --↑ serum homocysteine (B12 deficiency and Folate deficiency) !!

neoplasm back pain

metastases, multiple myeloma

Amyloid

misfolded protein that deposits in EXTRACELLULAR SPACE (outside of cell), thereby damaging tissues. Not one protein, it is a broad category, multiple proteins can deposit as amyloid. Usually have sinear, non-branching B-pleated sheet configuration. Stains pick up CONGO RED staining, and reveal APPLE GREEN birefringence when viewed micoscopically under polarized light. Tends to deposit around blood vessels. Can be deposited systemic (which can be primary, or secondary) or localized.

Hashimoto thyroiditis-

most common cause of hypothyroidism in areas of world with sufficient iodine. May initially present as hyperthyroidism (destroy thyroid and some leaks out into blood... but then hypo as cells die) Histologically defined by: - Lymphocytic infiltrate/chronic inflammation (!!) - Prominent germinal follicles/centers (!!) - Atrophic thyroid follices lined by Hürthle cells (epithelial cells with abundant, granular, deeply eosinophilic cytoplasm... turn pink). Because thyroid follicles are normally lined by low cuboidal epithelium, this is also known as Hürthle cell metaplasia.

Factor V "Leiden mutation"

most common cause or hereditary thrombophilia. The Leiden mutation is a single NT mutation in the Factor V gene which causes Arg → Gln (glutamine) substitution, makes factor V resistant to cleavage by protein C (and maybe S).... leads to inability to shut off factor V, increased activity of it, and hypercoaguable state.

etiology of iron deficiency

most commonly the result of chronic blood loss: menorrhagia, gastrointestinal bleeding (e.g. colonic polyp or cancer, Meckel's diverticulum in children). infants- breast feeding has little iron children- poor diet, Meckel's diverticulum Adults- peptic ulcer disease (males) menorrhagia (excessive menstruation) or pregnancy (females)

brunner's glands

mucus-secreting glands located in the deep mucosa and submucosa of the duodenum. . They are most numerous in the duodenal bulb and produce an alkaline secretions, mucus, pepsinogen, and urogastrone in response to acid stimulation.)

Colonic diverticula (aka diverticulosis)

multiple (often dozens) *colonic diverticula*. (Common in people > 60 years of age; 70% asymptomatic). these are *false diverticula* Occur where *vasa recta enter muscularis externa*—areas of intrinsic weakness. Due to chronic *↑ intraluminal pressure* from low-fiber diet (Western diet), hence the age-dependent prevalence Most commonly occurs in *sigmoid colon*

must know, hematopoiesis

multipotent hematopoietic stem cell divides into either: - common myeloid progenitor OR - common lymphoid progenitor Common myeloid progenitor can go into either: 1. Erythtoblast (RBCs) 2. Myeloblast (neutrophils, basophils, eosinophils) 3. Monoblast (monocytes) 4. Megakaryoblast (megakaryocytes Common lymphoid progenitor can go into either: - Natural killer cell - small lymphocyte (then B cell or T cell)

compartment syndrome

muscle groups of the human limbs are divided into sections, or compartments, formed by strong fascial membranes. • Compartment syndrome occurs when increased pressure within a compartment compromises the circulation and function of the tissues within that space. Acute compartment syndrome (ACS) usually develops soon after significant trauma, particularly involving long bone fractures. Causes: - fracture - thermal burns - injury to vascular structures - penetrating trauma -

Muscularis in GI tract

muscularis consists of smooth muscle that is generally found in two sheets: 1) an inner sheet of circular fibers 2) outer sheet of longitudinal fibers. Between the layers of the muscularis is a second plexus of neurons—*the myenteric plexus*.... this is *ESSENTIAL* for regulating BOTH GI motility AND ability to relax *LES*

Esophagus muscularis type

muscularis of the *upper 1/3* of the esophagus is *skeletal muscle*, the *intermediate 1/3* is *mixed* skeletal and smooth muscle, and the *inferior 1/3* is *smooth muscle*. Cotains *NANC- non-adrenergic, -non-cholinergic* neurons that release NO and vasoactive intestinal peptide to relax. At each end of the esophagus, the muscularis becomes slightly more prominent and forms two sphincters— the upper esophageal sphincter (UES) or valve, which consists of skeletal muscle and the lower esophageal sphincter (LES) or valve, which consists of smooth muscle.

concentric hypertrophy heart

n the case of chronic pressure overload, the chamber radius may not change; however, the wall thickness greatly increases as new sarcomeres are added in-parallel to existing sarcomeres. This type of ventricle is capable of generating greater forces and higher pressures, while the increased wall thickness maintains normal wall stress. This type of ventricle becomes "stiff" (i.e., compliance is reduced), which can impair filling and lead to diastolic dysfunction.

Hand changes in RA

narrowing of joint space and marginal erosions on both radial and ulnar aspects of the proximal phalanx. Ulnar drift of MCP joint pronation of wrist Swan neck deformity of fingers Boutonniere deformity thumb

Pyloric stenosis

narrowing of the pyloric canal due to *hypertrophy of the musculature*, most commonly in first born males. → obstruction (stenosis) → *nonbilious (!!) projectile vomiting* and demands to be re-fed soon *"hungry vomiter"*. (bile enters in duodenum) The pyloric stenosis usually develops between 2-6wks of age.... NOT right at birth! Exam may reveal an *"olive" (the hypertrophic pylorus) * in epigastrium Compare to duodenal atresia (distal to bile duct), which features vomiting of bile-stained fluid within 48hrs of birth.

17 hydroxylase

needed for pregnenalone to produce glucocorticoids, and sex steroids.... 17 hydroxylase deficiency leads to excess mineralcorticoids, no glucocorticoids or sex steroids. Males will be born with either feminized or completely female external genitalia and hypertension (from salt and water retention). Since female genitalia is the default pathway, females will appear sexually normal at birth. However, since androgens are essential to puberty, the females will present with a lack of secondary sexual development. Like the males, they will also have hypertension. Note: 11, 17 and 21 hydroxylase ALL interfere with glucocorticoid formation, so in ALL, we get excess ACTH and adrenal hyperplasia

Multiple myeloma and immunoglobulin

neoplastic plasma cells produce immunoglobulin, which elevates serum protein, so you test with serum-protein electrophoresis to determine the cause (S-PEP). Normally, there is: - a large albumin band - a1 band - a2 band - b band - gamma band (which is normally wide, not as high as albumin, represents gamma-globulins) In patient with multiple myeloma, since a plasma cell can only produce ONE antibody, there is a very high, sharp spike in the gamma region *(M-spike)* which indicates mono-clonial immunoglobulin, usually IgG, but can be IgA. NOTE: This is not the same M-protein associated with strep pyogenes!

CML- chronic myeloid leukemia

neoplastic proliferation of mature myeloid cells, especially granulocytes (especially basophils). Driven by Philadelphia chromosome: t(9;22), creating bcr-abl, a fusion gene with increased tyrosine kinase activity, which drives overproduction of neoplastic cells. 3 phaes: 1) chronic phase- Splenomegaly is common 2) Accelerated phase (spleen is becoming bigger) 3) transformation to Acute leukemia (AML 2/3 of the time, ALL 1/3 of the time... *patient has mutation in hematopoietic stem cell) Most cases result in blast crisis: number of blast forms ↑↑ and behaves like AML (short survival and rapid progression)

Chronic leukemia

neoplastic prolifferation of MATURE circulating lymphocytes, characterized by high WBC count. General Facts: Insidious in onset when compared to acute leukemias. Characterized by generalized, painless lymphadenopathy. Laboratory findings are similar to acute leukemia, except for blasts which are <10% in chronic leukemia.

features of acute anaphylaxis

neuro- dizziness, syncope nose- sneezing, runny nose upper airway- hoarseness, stridor, edema cardio- tacycardia, hypotension lower airway- chest tightness, ronchospasm skin- flushing, edema GI- nausea, vomiting, cramping

neutrophil rolling

neutrophils hit the selectins which act as 'speed bumps' on endothelial cells as they are expressed. They "roll" on the endothelial vessel. 2 kinds of selectins 1) P-selectin released from Weibel-Palade bodies, mediated by histamine. Weibel-Palade bodies contain 2 important proteins: P-Selectin, and (von) Willebrane factor. 2) E-selectin induced by TNF and IL-1 (!!!). Selectins bind "sialyl Lewis X" (!!) on leukocytes, which results in rolling of neutrophils/leukocytes along the vessel wall.

complications of peptic ulcer disease

never malignant in duodenal, rarely in gastric ulcers The complications of peptic ulcer disease are (1) bleeding, (2) perforation, (3) penetration into an adjacent structure, (4) obstruction from oedema or from scarring of the pylorus or duodenum, and (5) intractable pain.

Risk factors for atherosclerosis

non-modifiable - Family Hx is the most significant independent risk factor - ↑ Age - Male gender, postmenopausal women Modifiable (memorize!!!!) - Hypercholesterolemia - Hypertension - Smoking - Diabetes mellitus

hypertension categories

normal = <120/<80 pre-hypertension = 120-139/80-89 Stage 1 (moderate) 140-159/90-99 Stage 2 (severe)- >160/>100 a diagnosis is made when blood pressure is measured over two office visits

ectopic pregnancy presentation

pain, amenorrhea, and vaginal bleeding. palpable mass very low hCG

Lingual thyroid

persistence of thyroid tissue at base of tongue, presents as base of tongue mass.

Multiple myeloma

plasma cell neoplasm which is characterized by diffuse involvement of the skeleton. It is the most common PRIMARY malignancy of bone (most common malignancy to involve bone is actually metastatic carcinoma). MM is generally considered a disease of the elderly, with peak incidence occurring between ages 65-70.

causes of hemoptysis

pneumonia lung neoplasm pulmonary embolism TB foreign body over anticoagulation (warfarin)

gestational diabetes on mom and baby

pre-eclampsia (progress to eclampsia) - Diabetic retinopathy - - birth (neural tube) defects - Excessive body fat stores, stimulated by excessive glucose delivery during diabetic pregnancy, often extends into childhood and adult life. - Birth injury, including shoulder dystocia and brachial plexus trauma, are more common among infants of diabetic mothers, and macrosomic fetuses are at highest risk. Polycythemia • Hyperglycemia is a powerful stimulus to fetal erythropoietin production mediated by decreased fetal oxygen tension. Neonatal Hypoglycemia •Unrecognized postnatal hypoglycemia may lead to neonatal seizures, coma, and brain damage.

Burn management second deep and beyond

second (deep) and third degree: prevent sepsis (common: S aureus, P aeruginosa [most common cause of death green and distinctive smell] and C albicans) • Day 1-3: gram positive • Day 3-5: gram negative: proteus, klebsiella • Remove dead tissue • Skin graft: deep second or third degree burn that is > size of quarter -Fluid resuscitation: restore plasma volume and CO • Extra fluid if burn > 80% TBSA, 4 degree burn, electrical, inhalation (signs: facial burn, singed nasal hairs, soot, horseness, tachypnea, incr CO levels), paeds, delayed tx • Monitor urine output o Calculation (Parkland formula) - Requirements for 24 hours: 4mL x TBSA% x wt (kg) • 50% given in first 8 hours (consider from time of burn) • 50% given for next 16 hours

Presbycusis

sensorineural hearing loss associated with age, affects high frequency sounds more. Usually due to impaired blood supply to the ear, but also the loss of ear hair cells.

Hypoalbuminemia in nephrotic syndrome

serum albumin < 3g/dL (the lower limit of normal is 3.4g/dL). Hypoalbuminemia results in ↓ plasma colloid oncotic pressure → compensatory ↑ in α2-macroglobulin synthesis to maintain oncotic pressure. The *hypoalbuminemia and the resultant ↓ in plasma colloid oncotic pressure.* also causes Generalized *pitting edema *(anasarca if severe)— This generalized edema is further aggravated by ↑ Na and H2O retention due to *hypovolemia*: - Compensatory aldosterone secretion (hypovolemia → ↑ renin → ↑ angiotensin II → ↑ aldosterone) - Sympathetic stimulation (hypovolemia → ↑ SNS outflow) - ↓ Natriuresis (hypovolemia → ↓ atrial natriuretic peptide → ↓ Na excretion)

Short vs long term BP regulation

short = Baroreceptor long = RAAS

complications of labor

shoulder dyslocation meconium aspiration Post-Partum Haemorrhage (PPH) -

Rb mutations

since it is a *tumor supressor gene*, BOTH copies must be knocked out. Sporatic mutations likely to lead to unilateral retinoblastoma (tumor in back of eye) Germline (familial) mutations likely to lead to bilateral retinoblastoma and osteosarcoma. Rb protein: 'Rb protein is a *tumor supressor* gene which normally is *bound to E2F*. Transition from G1 to S *can only happen* when* transcription factor E2F* is unbound from Rb, and is *free in the nucleus*. *cyclins*, such as *cyclin D1* function as regulators of CDKs (Cyclin-dependent kinases). Cyclin D1 binds to CDK4 OR CDK6, and forms a *cyclinD1-CDK 4or6 complex*, and this complex *inhibiting the tumor supressive activity of Rb*. It does this *phosphorlation of Rb* by the *CyclinD1-CDK 4or6 complex*, and forming *phosphorylated Rb (P-Rb)* *Phosphorylated Rb* is no longer able to hold the *transcription factor* called *E2F. E2F is released, makes it 'free', and allows cell to progress from *G1--> S phase.* *mutated* Rb causes an overexpression of CDK4&CDK6 or cyclin D1, causing excess phosphorylation of Rb, excess release of E2F, and thus the cell is *NOT* arrested in the checkpoint after G1 and before S. Note: since Rb is also a *tumor supressor gene*, BOTH copies must be knocked out.

Small cell carcinoma treatment

small cell lung carcinomas are highly mitotic and undifferentiated, they are very sensitive to radiation and chemotherapy treatments. however, due to it's aggressive nature, small cell lung carcinomas are often distantly metastatic at the time of discovery. Even with treatment, prognosis is grim - mean survival after diagnosis is only 1 year. Patients with small cell lung carcinoma are NOT surgical candidates.

Graves clinical findings

• 1) Hyperthyroidism secondary to diffuse, symmetrical, nontender hyperfunctional enlargement of the thyroid • 2) Infiltrative ophthalmopathy: - exophthalmos (proptosis) due to accumulation of glycosaminoglycans and adipose in retro-orbital tissue; this occurs in ~50% of patients - extraocular muscle weakness • 3) Infiltrative dermopathy: - pretibial myxedema: scaly thickening and induration of the skin overlying the shins with nonpitting edema; this only occurs in 1-2% of patients

Treatment of hyperthyroidism:

• 1) β-blocker to control symptoms of ↑ SNS tone • 2) Thioamide — e.g., PTU (propylthiouracil), methimazole: - May induce remission by blocking new thyroid hormone production via inhibition of the organification and coupling steps of thyroid hormone synthesis. - PTU (not methimazole) also inhibits peripheral conversion of T4 to T3. • 3) High-dose iodine → blocks release of T4 and T3 into the circulation • 4) High-dose radioactive iodine 131I (versus the 123I used in imaging studies) → becomes concentrated in the thyroid gland → ablation of thyroid function

4. Outline those factors that determine burn severity and those that predict a poorer prognosis.

• Age: more complications if <3 or >60y/o • Depth degree: etiology and time of exposure • Location: special care for face, neck, hands, feet, perineum • Inhalation: resp system • Associated injuries: eg. fractures • Co-morbid factors: eg. disability, alcoholism, seizure disorder

IgE

• Before binding to antigen, IgE binds tightly to Fc receptors on basophils and mast cells — thus, it is the least common Ig in serum. • Once bound to the Fc receptors on basophils and mast cells, binding of cognate antigen (e.g., allergens) by IgE triggers release of cytokines and other mediators involved in the allergic response — this is a Type 1HSR (hypersensitivity reaction). • During an infection with invasive helminths, IgE mediates an ADCC (antibody-dependent cell-mediated cytotoxicity) response: IgE binds to the surface of the helminth → eosinophils (which have Fc receptors for IgE) bind to the free Fc "tail" of the IgE, triggering eosinophil degranulation → release of cytotoxic mediators (e.g., lytic enzymes, perforin, granzymes, tumor necrosis factor) to try to kill the helminth.

2nd and 3rd trimester bleeding

• Bloody show associated w/ cervical insufficiency or labour • Placenta Previa • Abruptio placenta • Uterine rupture

Anorexia Nervosa

• Characterized by a body weight less than 85% of that expected, with intense fear of gaining weight or becoming fat, even though underweight (they usually have normal appetite) May be further divided into 2 subtypes: • Restrictive (severe limitation of food intake is the primary means to weight loss) • Binge-eating/purging (periods of food intake are compensated by self-induced vomiting, laxative or diuretic abuse, and/or excessive exercise) • Associated with severe weight loss, metatarsal fractures, amenorrhea, anemia, and electrolyte disturbances • Commonly coexists with depression • Treatment for this life-threatening condition initially involves hospitalization to restore a good nutritional status. Antidepressants (especially Mirtazipine because of weight gain side effects) and family therapy are also useful

Bulimia Nervosa

• Characterized by binge eating followed by vomiting or abuse of laxatives, diuretics, or enemas. Also associated with excessive exercising • Body weight is usually normal or slightly overweight. • Associated with esophageal tears (Mallory-Weiss syndrome) and rupture (Boerhaave syndrome), dental caries, swelling of parotid glands, electrolyte disturbances, menstrual irregularities, alkalosis, and dorsal hand calluses from inducing vomiting (Russell's sign)

complications of a PE

• Clot may completely occlude a pulmonary artery → parenchymal ischemia → hemorrhagic infarction • Higher perfusion (not oxygenation) to the lower lobes of the lung → more chance that a PE will go to the bases → infarction is most likely in the bases

cocaine

• Cocaine blocks the presynaptic reuptake of serotonin and catecholamines. • Cocaine is a stimulant of alpha-1, alpha-2, beta-1, and beta-2 adrenergic receptors. The stimulation of alpha receptors cause vasoconstriction in cardiac and peripheral vasculature. • Cocaine slows or blocks sodium channels manifesting clinically as negative inotropy. • Cocaine increases the brain activity of glutamate and aspartate which are each excitatory amino acids.

HLA: Human Leukocyte Antigen Classes

• Consists of three classes of molecules (Major Histocompatibility I, II, and III) • Discriminates between self and nonself. Also involved in antigen presentation to T cells by self-MHC restriction (antigens can only be presented to T cells with the same HLA type). • Specific HLAs are associated with various immunologic disorders and susceptibility to infectious agents

Diagnose PE

• Definitive diagnosis is made with Pulmonary CT angiogram, which shows obstructed vessel • D-Dimer: this important lab test is used in the evaluation of a potential PE. A negative D-Dimer is a good prognostic sign that a PE is not present. A high level after treatment may be used to assess for the risk of recurrent DVT/PE.

types of schizo

• Disorganized: disinhibited, disorganized, poor personal appearance, inappropriate emotional response. Onset before 25 years of age • Catatonic: stupor or agitation, waxy flexibility (patient will hold any posture that he is placed in, similar to a wax figure); rare since the introduction of antipsychotic agents • Paranoid: delusions of persecution or grandeur; better social functioning and older age at onset than other subtypes • Undifferentiated: characteristics of more than one subtype • Residual: one psychotic episode with subsequent flat affect, illogical thinking, odd behavior, and social withdrawal (residual symptoms)

types of estrogen

• Estradiol (17B-estradiol) is most potent estrogen produced and excreted by ovary o Principle estrogen in premenopausal woman • Estrone is a metabolite of estradiol that has 1/3 the potency o Estrone is primary circulating estrogen after menopause and is generated mainly from conversion of androstenedione in peripheral tissues • Estriol another metabolite is significantly less potent o present in significant amounts during pregnancy, because principal estrogen produced by placenta

Major Histocompatibility Complex-I (MHC-I) and APC

• Expressed on virtually all cells and usually present antigens that are *intracellular* 1. Digestion of antigen into peptide fragments *within* infected cell. 2) Infected cell synthesized MHC-I molecules at the ER 3) Antigen peptide fragments enter ER and bind to MHC-1 4) Antigen-MHC-1 molecules packed into vesicles 5) The vesicles undergo exocytosis and are inserted on the plasma membrane. Each class I HLA protein pairs with another protein called β2-microglobulin to make up the complete class I MHC molecule. • β2 microglobulin is necessary for cell surface expression of MHC-I. Note: β2 microglobulin is not expressed on RBCs

ARMD

• Exudative ("wet") ARMD (less common): causes sudden visual loss due to leakage of serous fluid into the retina, followed by abnormal vessel formation (neovascularization, hence "wet") under retinal pigment epithelium Nonexudative ("dry") ARMD: atrophy and degeneration of central retinal pigment epithelial layer below the retina, which causes vision loss through loss of photoreceptors

functions of thyroid hormone

• For thyroid hormone functions, remember the 4 B's. Brain maturation Bone growth Beta-adrenergic effects BMR ↑

Hallucination vs illusion vs delusion

• Hallucination - false sensory perception in the absence of actual stimulus (e.g. A man hears the voice of his dead wife talking to him) • Illusion - inaccurate perception of real existing sensory stimuli (e.g. ie, body dysmorphic disorder) . delusion- Fixed, false beliefs... cannot be corrected by logic, and NOT consistent with culture and education of the patient,

IgG:

• IgG and IgM are capable of activating the classical pathway of the complement cascade (IgM does it better) Can cross placenta Capable of opsonization

IgM

• IgM = first Ig made by a B cell following the first exposure of that B cell to its cognate antigen. • Pentameric structure (5 IgMs held together by a J-chain → 10 total antigen binding sites!) of the secreted form of IgM makes it the most efficient at: - agglutinating Ig - activating the classical pathway of the complement cascade

IgA

• In serum, IgA exists as a monomer. In mucosal secretions, IgA exists dimer • As the most abundant Ig class in mucosal secretions by far, it comes as no surprise that the primary function of IgA = protective defense of the mucosa of the respiratory, digestive, and urogenital systems against toxins and microbial pathogens

androgen insensitivity

• In these subjects there is an absence of androgen receptors. • Thus, testes develop normally (under the influence of the XY chromosome), but do not descend • Mullerian inhibitory hormone is produced and the female tract regresses. •Testosterone levels are normal but they cannot exert an effect as there are no receptors, thus the Wolffian tract and the external male genitalia do not develop. • The phenotype is therefore female o Under the influence of testicular and adrenal oestrogens, at puberty, breast development and the female pattern of fat deposition occurs. • The brain in these individuals has been 'feminised' and so they appear, feel and behave female.

Lifestyle modifications for Hepatitis

• It's important to eat a well-balanced diet, as the build up of fatty deposits in the liver can damage it further • As hepatitis C can lead to cirrhosis (scarring) of the liver, liver cancer or liver failure, it's advisable not to drink alcohol

omalizumab

• Monoclonal antibody to IgE • Prevents binding of IgE to FCεR1 by binding IgE • License: IgE-mediated asthma

negative schizo symptoms

• Negative symptoms include: - flattening of affect - thought blocking (sudden halt in train of thought) - deficiencies in speech content - cognitive disturbances - poor grooming - lack of motivation - social withdrawal

Outline features of a burn of its mechanism of injury that would raise the possibility of neglect or non-accidental injury as possible cause or contributing factor

• Obvious pattern from cigarettes, lighters, irons • Burns to soles, palms, genitalia, buttocks, perineum • Doughnut sign, area of spared skin surrounded by scald eg. child held to bottom bath there skin won't burn that's forced against the bath • Other signs of abuse

Systemic response to burns

• Occurs when 30% of total body surface area (TBSA) is burned . cytokines etc systemic manifestations and response to burn injury begins with systemic inflammatory response syndrome (SIRS) and the release of mediators. Vasoactive substances are released along with the stress hormones cortisol, glucagon, and epinephrine. The local and systemic responses produce the hallmark factors that are identified with burn injuries. Fluid shifts from blood to interstitial and intracellular spaces that lead to marked edema formation due to the decreased capillary oncotic pressure and increased interstitial oncotic pressure. Tissue edema that may lead to airway instability, respiratory failure, limb ischemia, and compartment syndromes. Hemoconcentration due to increase blood viscosity Decreased intravascular volume that leads to severe hypovolemia that lead to the need for significant fluid resuscitation Burn hypermetabolism which causes increased oxygen consumption, negative nitrogen and potassium balance, excessive muscle wasting, glucose intolerance, hyperinsulinemia, insulin resistance, sodium retention, and peripheral leukocytosis

Types of glaucoma

• Open (wide) angle glaucoma (accounts for 90% of cases): characterized by impaired outflow (e.g. Schlemm's canal) of aqueous humor and *absence of symptoms* can lead to silent progression. *Primary open-angle glaucoma* - genetic disorder - mutation in MYOC gene *Secondary open-angle glaucoma*- senescent red cells after trauma (ghost cell glaucoma), iris epithelial pigment granules (pigmentary glaucoma), fragments of oxytalan fibers (exfoliation glaucoma), and necrotic tumors (melanomalytic glaucoma) can *clog the trabecular meshwork* • Closed angle glaucoma: characterized by occlusion of flow between the *iris and lens*, resulting in rapid increase in IOP. *Ophthalmologic emergency* that leads to irreversible vision loss within hours if left untreated. • Congenital glaucoma: developmental defect in the structure of the anterior chamber, associated with Sturge-Weber, neurofibromatosis type I, and Marfan's syndrome

Post partum depression

• Postpartum depression occurs in 10-15% of women in the general population. Postpartum depression occurs most frequently in the first 4 months following delivery, but can occur anytime in the first year. •women at highest risk are those with a personal history of depression, previous episode of postpartum depression, lack of social support, etc • Postpartum depression is more persistent and debilitating than postpartum blues. Symptoms of major depression may include: • Depressed mood, • Tearfulness, • Insomnia, • Fatigue, • Appetite disturbance, • Suicidal thoughts, and recurrent thoughts of death. • In the postpartum period, depression is characterized as intense sadness, anxiety, or despair. These interfere with the mother's ability to function with risk of harm to mother or infant.

Major Histocompatibility Complex-II (MHC-II) and APC

• Primarily found on cell membranes of APCs , MHC-II proteins present antigens from *extracellular organisms*. 1) APC's (phagocytic cells like dendritic cells and macrophages, or B lymphocytes) ingest antigen by phagocytosis/endocytosis. 2) Antigen digested into peptide fragments within the phagosome or endosome. 3) APC synthesizes the MHC-II molecules, and packages them into vesicles. 4) Vesicles containing antigen peptide fragments and MHC II 's fuse 5) Peptide fragments bind to MHC-II. 6) antigen-MHC II complex undergoes exocytosis and is inserted onto plasma membrane to present to CD4+ Th- cells. • Encoded by the following Human Leukocyte Antigen (HLA) genes: HLA-DR, HLA-DP, HLA-DQ

prolactin

• Prolactin levels rise throughout pregnancy reaching a maximum at parturition, because estrogen stimulates prolactin. (but est and progest block the action of prolactin on the breast) suckling increases both oxytocin and prolactin prolactin inhibits ovulation by inhibiting GnRH release by hypothalamus. Inhibits GnRH action on anterior pituitary. Antagonizes LH/FSH on ovaries. Prolactin and Oxytocin are both stimulated by afferents from the nipple. - Prolactin sustains milk production - Oxytocin causes milk let-down. Suckling during breast-feeding initiates sensory impules from receptors in the nipple to the hypothalamus, causing inhibition of prolactin-inhibiting factor, and prolactin is released from the anterior pituitary.

Rods vs cones

• Rods and cones are photoreceptors that generate graded potentials in response to light. -Rods: Important for night vision, more evenly distributed throughout the retina. -Cones: Concentrated in the fovea centralis, important for day, color, and high acuity vision. • Rods and cones → bipolar cells → retinal ganglion cells → CN II → optic chiasm → optic tract → lateral geniculate body → visual cortex (Brodmann's area 17)

Virchow's triad

• Stasis: Blood clots when it flows slowly → hospitalized /immobile patients are at a greater risk for DVT formation • Hypercoagulability: Can be the result of inheritable conditions such as Factor V Leiden (Factor V is not appropriately inactivated) or Protein C deficiency. Can also result from acquired conditions such as antiphospholipid syndrome, pregnancy and post-operative state. Any condition increasing the probability of thrombus formation can potentially lead to a DVT or PE • Endothelial Damage: Injury to vessel walls expose platelets to subendothelial collagen → clot formation. For example, surgical patients and DIC patients have endothelial damage

TH1 vs TH2

• Th1 cells coordinate a *cell-mediated immune response to eradicate intracellular pathogens * (ie mycobacteria) 1. Intracellular pathogens stimulate a strong innate immune response. Macrophages (release IL-12) and NK r(release IFN-y) cells induce differentiation of pleuripotent Th0 cells into Th1 cells! 2. Th1 cells secrete IL-2, IFN-γ, TNF-α, and TNF-β 3. IFN-γ produced by Th1 cells promotes macrophage activation and further development of Th1 cells 4. Proliferation of Th1 cells is inhibited by IL-4 and IL-10 produced by Th2 cells.

TH2 cells

• Th2 cells coordinate a *humoral (antibody) response to extracellular pathogens (eg, helminths) and allergens:* !! 1. Extracellular pathogens and allergens do not stimulate a strong innate immune response involving macrophages and NK cells (only intracellular) differentiation of pleuripotent Th0 cells into Th2 cells is the default pathway and is driven by constitutive elaboration of IL-4 by the naive Th0 cells themselves (!!) 2. Th2 cells secrete IL-4, IL-5, IL-6, IL-10, IL-13, and TGFβ 3. IL-4 and IL-10 produced by Th2 cells promote further development of Th2 cells. (inhibit Th1) 4. Proliferation of Th2 cells is inhibited by IFN-γ produced by Th1 cells. • Th2 cells help B cells make antibodies: - Th2 cells are essential for IgE production - Th2 cells also help stimulate production of IgG and IgA (IL-5)

cervical smear test

• The Pap test aims to identify abnormal cells sampled from the transformation zone, the junction of the ecto- and endocervix, where cervical dysplasia and cancers arise. The collected specimen can also be used for other diagnostic assessments (i.e. testing for gonorrhea, chlamydia, and HPV).

Active Immunity

• The acquired host immune response that arises after exposure to a foreign agent such as an infection or a vaccination, usually involves both cell-mediated and humoral immunity. • Memory B and T cells develop after initial exposure to foreign antigens → reinfection rapidly activates these memory cells • Usually lasts for the lifetime of the patient, but vaccine-induced immunity can wane over time

causes of gestational diabetes

• The resistance stems from placental secretion of diabetogenic hormones including: • Growth hormone, • Corticotropin releasing hormone, • Placental lactogen, • Progesterone, as well as: • Increased maternal adipose deposition, • Decreased exercise, • Increased caloric intake.

Passive Immunity

• The transfer of active humoral immunity (e.g. antibodies) from one individual to another (e.g. IVIG infusions) • Not produced by the patient's body, → immunity persists only as long as the antibodies are in the body. • Other examples of passive immunity: human tetanus immune globulin given to treat tetanus, a baby receiving antibodies in his mother's breast milk

Pseudohermaphrodites

• These are individuals with entirely male or female gonads but in whom the external and/or internal appearance is abnormal. Male pseudohermaphrodites are 46XY and may have: • Female Genitalia • Ambiguous genitalia • Persistant Müllerian ducts Female pseudohermaphrodites have: • Normal 46XX • But have masculinisation of the external genitalia usually due to exposure to high levels of androgens in utero prior to 12 weeks. • By far the most common cause is the absence of 5a-reductase, which means there is no DHT. • This results in normal development of the internal male system, but the external genitalia are not fully masculinized and the neonate is taken for a female. • At puberty, testosterone levels are high and induce 5a-reductase and so stimulation of the external genitalia occurs along with the other secondary sex characteristics causing masculinisation.

Congenital Adrenal Hyperplasia

• This is absence of 21-hydroxylase in the adrenal (converts adrenal androgens to cortisol). • Negative feedback effect on ACTH lost. • Levels of ACTH are high and stimulate adrenal hyperplasia and excessive adrenal androgen production which in females causes masculinization of the external genitalia. • These subjects have normal internal reproductive tracts and surgery is usually employed.

Head injury

• Traumatic brain injury may be divided into primary injury and secondary injury. • Primary injury is induced by mechanical force and occurs at the moment of injury. • Secondary injury is not mechanically induced. It may be delayed from the moment of impact, and it may superimpose injury on a brain already affected by a mechanical injury. • Head injuries may be closed or open. A closed (non-missile) head injury is where the dura mater remains intact

symptoms of menopause

• Vasomotor symptoms - i.e. hot flushes, night sweats and palpitations and this occurs in majority of women. It is due to fluctuations in oestrogen. • CNS symptoms - i.e. mood changes, irritability, depression, sleep disturbances, loss of libido. 2) Local (all due to low oestrogen) • Vaginal dryness • Dyspareunia (painful intercourse) • Urinary tract infections • Urinary incontinence

wheeze vs stridor

• Wheezing • *Whistling sound* produced by vibration of opposing walls of *an airway that is narrowed* almost to the point of closure. • Stridor • *Inspirator*, Even more strident, urgent, harsh noise. • Indicates *extreme difficulty with breathing.*

chronic renal failure and ions

↑ anion gap *metabolic acidosis* due to: 1) *↓ renal excretion of H as NH4* (hence the metabolic acidosis) .... (note, this is partially due to *calcium buffering* as calcium seeps from bone) 2) ↓ renal excretion of sulfate, phosphate, urate, hippurate, etc. (hence the ↑ anion gap) *↓ 1-α-hydroxylase* (in PCT!!)→ ↓ 1,25-dihydroxyvitamin D production → ↓ reabsorption of Ca from GI tract → *hypocalcemia* → secondary hyperparathyroidism *(↑ PTH)* → ↑ bone turnover → resorptive cystic bone lesions (*osteitis fibrosa cystica*, which is a type of renal osteodystrophy) Retention of Na and H2O → *hypertension* and *accelerated atherosclerosis*, peripheral edema, congestive heart failure ↓ renal excretion of phosphate → *hyperphosphatemia*, which also contributes to the *hypocalcemia* by *combining with calcium to precipitate* out into tissues (metastatic calcification) ↓ renal excretion of Mg → *hypermagnesemia* ↓ renal excretion of K →* hyperkalemia*(peaked T waves on EKG) → 1) inhibits NH3 synthesis in proximal tubule → ↓ renal excretion of H as NH4 Hyperkalemia can also be aggravated by insulin deficiency (recall that insulin causes the transcellular shift of K → into cells).

Potassium sparing diuretic side effects

→ overdose or supratherapeutic levels of K sparing diuretics can lead to *hyperkalemia* (vs. loops and thiazides, which can cause *hypokalemia*

Prerenal azotemia (prerenal AKI)

↓ blood flow to kidney, kidneys are intrinsically normal ↓ Blood flow to kidney (*without* parenchymal damage) → ↓ GFR get a *azotemia*, so BUN and Creatinine both rise. However, the *ratio* of BUN:Creatinine is critical for determining the cause. Normally, some BUN returns to blood, but creatine does *not* have ability to be reabsorbed. Normal BUN:creatinine ratio is 15. In pre-renal AKI, this ↑ RAAS and aldosterone causes ↑ Reabsorption of Na and H2O... as this happens, addional BUN flows into blood, so *BUN:creatine > 15!!* Since kidney parenchyma and tubular function (concentrating ability) *are intact* we have a *FENa < 1%* (sodium still resorbed) and *urine osmolality > 500* (tubules *can still concentrate* urine) Note, there is efferent arteriole vasoconstriction → preserves some GFR (still lower than normal)

ST segment

■ is isoelectric. ■ represents the period when the ventricles are depolarized.

QT interval

■ is the interval from the beginning of the Q wave to the end of the T wave. ■ represents the entire period of depolarization and repolarization of the ventricles.

P wave

■ represents atrial depolarization.

Expiratory reserve volume

amount of air that can be *expired* beyond a normal breath

inspiratory reserve volume

amount of air that can be inspired *beyond* a normal breath

findings of systemic amyloidosis.

amyloid can deposit anywhere, but kidney is the most commonly involved organ, and it usually results in nephrotic syndrome (large loss of protein in urine). Also heart, leads to restrictive cardiomyopathy/arrhythmia. Tongue inlarged, bowel thickened (malabsorption), liver/spleed. Amyloid CANNOT be removed, requires transplant if excessive.

first degree burns

o First (Erythema/superficial/epidermal) eg. sunburn - Depth: epidermis PINK - CF: painful, sens intact, erythema, no blisters, cap refill

pregnancy hyperthyroidism risks

preterm delivery low birth weight IUGR, stillbirth fetal thyroid distruction (think IgG connection crossing placenta) increased perinatal mortality.

RAST test

(Radio AllergoSorbent Test) is a 'test-tube' detection system which originally used a radiolabel to identify specific IgE antibodies to various environmental and food allergens present in a blood sample. • For example, if the patient is allergic to dust mites, the dust mite IgE will be raised.

Corticosteroids asthma

(beclomethasone, triamcinolone): Systemic corticosteroids (either PO or IV) are often used in the treatment of asthma *exacerbations* Interact with *nuclear* steroid receptors to decrease production of *phospholipase A2* and *NFκ-β* → ↓ production of inflammatory agents Also increases transcription of β2 receptors in the airways.

Lack of Protein C or S

(these proteins NORMALLY inactivate factors V and VIII in clotting cascade, which amplify clotting cascade.... so lack of proteins C and S mean more amplification by factors V and VIII.... note, risk for Warfarin skin necrosis (feared complication)

Aortic stenosis murmur

*mid systolic* ejection "click" followed by a crescendo-decrescendo murmur... it *radiating to the carotids* Heard loudest at *second intercostal space at the right sternal border* S4 heart sound present: ↓ intensity with ↓ preload (ie, valsalva maneuver) ...and ↑ intensity with ↑ preload

Aortic stenosis overview

*narrowing* of aortic valve orifice. Usually due to fibrosis and calcification from "wear and tear". Presents in late adulthood (>60)... increased risk with congenital *bicuspid* aortic value (because most people normally have 3 cusps for aortic valve). Can also occur from *chronic rheumatic valve disease*..... but note that aortic valve disease always starts in the *mitral* valve. So, the presence of co-existing *mitral stenosis* and *fusions of aortic valve commissures* (also in rheumatic) distinguish this from normal "wear and tear".

Crohns disease

-Unclear (infection?) etiology -Transmural inflammation - SKIP lesions in ANY portion of GI tract, mouth to anus - Noncaseating GRAULOMAS and lymphoid aggregates (Th1 mediated) - SMOKING increases risk - Strictures (dense fibrosis lead to obstruction and reduction of lumen... also *creeping fat*), - May or may not have bloody diarrhea - *COBBLESTONE* musoca- - *RIGHT* lower quadrant pain

Dysfunctional uterine bleeding

-anovulatory cycle (70%) The ovary produces estrogen, but no corpus luteum is formed. Without the corpus luteum, progesterone is not produced. This prevents the usual withdrawal bleeding. The continuously high estrogen continues to stimulate growth of the endometrium. Bleeding occurs only once the endometrium outgrows the blood supply. Second most common is PCOS. Other causes include: - pregnancy - uterine fibroids -endocrine producing neoplasms -endometrial carcinoma - coagulation defects - trauma/abuse

ways to investigate colon cancer

DRE sigmoidoscopy colonoscopy barium enema fecal occult blood testing

Bcl2 is on chromosome

18

O2 curve shift left

4 factors cause O2 dissociation (T form favored): 1) ↓ pH: relative acidic environment, like peripheral tissues 2) CO2: produced by cellular metabolism 3) 2,3-DPG (diphosphoglycerate, the same as bisphosphoglycerate): stabilizes the T conformation, produced by glycolysis 4) ↑ temperature These factors shift the O2 dissociation curve to the right - a higher O2 pressure is needed to maintain the same level of hemoglobin saturation

emphyema

A collection of pus in the pleural space is known as Empyema.

spondylosis

A degenerative osteoarthritis of the vertebrae with nodular bone formation. Frequently causes narrowing of the intervertebral foramen and compression of exiting spinal nerves. Usually in cervical region in elderly.

dementia cholesterol disorder

A genetic locus on chromosome 19 encodes for a cholesterol transporter called apolipoprotein E (apoE), which increases deposition of fibrillar beta-amyloid

Types of diutetics

Acting from most proximal to most distal!! 1. Carbonic anhydrase inhibitors 2. osmotic agents 3. Loop Diuretics 4. Thiazide diuretics: 5. K-sparing diuretics

Hep B pre core mutant

A precore mutant is a variety of hepatitis B virus that does not produce hepatitis B virus e antigen (HBeAg)] These mutants are important because infections caused by these viruses are difficult to treat, and can cause infections of prolonged duration and with a higher risk of liver cirrhosis

hemorrhagic vs pale infarct

A pulmonary infarct is hemorrhagic because of the dual blood supply from the non-occluded bronchial arteries which continue to supply blood, but do not prevent the infarction. White infarct = end arteries (eg Heart, spleen, kidneys)

Which hepatitis virus' have a vaccine

A, B (and thus D)

Virus' that cause hepatitis

A, B, C, D, E Other viruses may also cause it, such as those that cause mononucleosis (the Epstein-Barr virus) or chickenpox (the varicella virus).

A band

A-band - myosin filaments which may overlap with actin filaments does NOT change in length on contraction

Mucosa mucsularis

A thin layer of smooth muscle fibers called the muscularis mucosae throws the mucous membrane of the stomach and small intestine into many small folds, which increase the surface area for digestion and absorption

Functional residual capacity

Air not *normally* exhaled. so it is ERV + RV

small cell carcinoma

ALL small cell lung carcinomas are high grade, highly malignant and *widely metastatic. Small cell lung carcinomas are the *most aggressive* of all lung carcinomas Extensive necrosis is common in small cell lung carcinoma. Small cell lung cancer, like *squamous cell lung cancer*, more commonly *arises centrally* near the hilum or major bronchi Mnemonic: when it starts with "S" it is associated with Smoking, central, and maybe paraneoplastic syndrome.

Leukocyte adhesion deficiency

AR defect of integrins (C18 subunit) essential β2-integrin on lymphocytes, macrophages, and neutrophils Clinical features: delayed separation of umbilical cord within first few weeks of life!! (normally it dies, falls off via necrosis via inflammation/neutrophils). Increased circulating neutrophils (leukocytosis, 6-10x normal) Recurrent bacterial infections that LACK PUS in conditions such as: Abscesses, Omphalitis, Pneumonia, Gingivitis, Peritonitis

complications of bulemia

Abdominal pain and bloating • Heme-stained emesis • Mallory-Weiss syndrome (esophageal tears) • Esophageal rupture (Boerhaavesʼ syndrome) • Gastroesophageal reflux disease (GERD)

Renal agenesis

Absence of kidney formation, can be either unilateral or bilateral. unilateral agenesis leads to *hypertrophy of other* kidney... but as it hypertrophies, it increases risk for hyperfiltration later in life. *bilateral* agenesis failure of fetal renal excretion → *oligohydramnios (↓ amniotic fluid)* !!!→ multiple anomalies (*Potter phenotype*) and early death:

Mitral regurge presentation

Acute disease presents with the rapid onset of severe congestive heart failure and a low cardiac output state, and is commonly due to papillary muscle rupture. Patients with chronic mitral regurgitation may be asymptomatic with normal exercise tolerance. However, they are often sensitive to shifts in volume status and may be at risk for development of volume overload and right-sided heart failure. Acute cases present with *jugular venous distension* and signs of congestive heart failure on physical exam, while chronic disease presents with an apical thrill without signs of congestive heart failure.

mature t-cell neoplasms

Adult T cell leukemia/lymphoma - Enteropathy-associated T-cell lymphoma -Aggressive NK-cell leukemia

types of dementia

Alzheimer's disease, vascular disease neurosyphilis dementia with Lewy bodies pick's disease .

What controls peripheral resistance?

As the vessels of highest resistance, the arterioles are primarily responsible for the physiological parameter of *total peripheral resistance (TPR)*, which determines the slope of the venous return curve.

Treat acute MI

Aspirin/heparin - limit thrombosis Supplemental O2 nitrates (vasodilate) B-blocker ACE inhibitor

Squamous cell carcinoma paraneoplasm

Associated with paraneoplastic syndrome producing *hyperparathyroidism* via ectopic *PTHrP* ( (parathyroid hormone related peptide) production..... leads to *hypercalcemia* of malignancy.

Cryptorchidism consequences

Association with inguinal hernia in about 10% to 20% of cases Sterility (if bilateral). Infertility in uncorrected unilateral cryptorchidism (because the contralateral descended testis may also be deficient in germ cells). Risk of testicular cancer (undescended testis) Defect in testicular development and cellular differentiation that is unrelated to anatomic position.

3 main risk factors for ischemic heart diease

Atherosclerotic narrowing of a coronary blood vessel Thrombus formation in a coronary blood vessel Coronary vasospasms such as those seen in prinzmetal angina pectoris.

Bilirubin metabolism

Bilirubin is the *yellow* breakdown produce of old RBC's. RBC's live 120 days, macrophages of reticuloendothelial system (particularly in spleen) break down RBCs and its hemoglobin into heme+globin (Globin broken down to AA's) Heme broken down to iron and biliverdin Iron recycled, biliverdin converted to unconjugated bilirubin (UCB), which is taken by albumin to liver where it is conjugated (CB) with glucuronic acid and dumped into bile canniculi, then bile duct, then gallbladder to be stored.

Basophils

Bilobed nucleus. Intracellular granules stain well with basic dyes, hence "basophilic" Granules contain: Heparin Histamine → key role in mediating allergic reactions Leukotrienes and cytokines are synthesized on demand

Treat osteoporosis

Bisphosphonates- Raloxifene (SERM) Pulsatile PTH Calcitonin Denosumab Also Ca/Vit D.

cystitis

Bladder inflammation (part of the lower urinary tract) from fecal flora, drugs, and/or radiation. Presents as dysuria, urinary frequency, urgency, and suprapubic pain.... NO systemic findings (fever, chills, night sweats, etc) Vast majority (80%) *E.Coli*

Metrorrhagia

Bleeding between menstrual periods

Menometrorrhagia

Bleeding which is too heavy/prolonged AND occurs more frequently

Hep C transmission

Blood, IVDU (especially w/HIV)

comminuted fracture

Bone is splintered/crushed at site of impact, so smaller bone fragments lie between two main fragments

Type 1 collagen

Bone, tendon, skin, fascia, late scar tissue, cornea Is very strong. Involved in Osteogenesis imperfecta: Defect in collagen synthesis → weak bones → easily fractured. Symptoms also include classic finding of blue sclera and hearing loss (middle ear bone abnormalities). It is often confused with child abuse. Also Ehlers-Danlos Syndrome: Hyperelastic skin, hypermobile joints

adenoma vs carcinoma!!

Both are tumors that develop from epithelial cells (Cells that have a free surface on one side and are attached to tissue on the other side and contain no blood vessels). Epithelial cells line most glands and organs and the skin. An adenoma is a specific kind of benign (non cancerous) tumor that starts on a gland or organ. While an adenoma is benign sometimes, however, adenomas develop into malignancies. When this happens, the newly malignant adenoma is called an adenocarcinoma. A carcinoma is any cancerous tumor that develops from any epithelial cells.

number of vertebrae

C-7 T-12 L-5 S-5 (fused) C4 (fused

name mature B cell neoplasms

CLL Hairy cell leukemia Multiple myeloma MALToma

diagnose mitral stenosis

CXR will show a dilated left atrium with straightening of the left heart border and elevation of the mainstem bronchus due to mass effect of the enlarged atrium. Echocardiography is necessary to confirm and stage disease, and will show left atrial enlargement, with or without right ventricular enlargement, and valvular calcification, and can be used to calculate:

Diagnose pneumonia

CXR, sputum gram stain and culture, and blood culture.

Chronic bronchitis Xray

CXR: prominent vessels, large heart and moderate hyperinflation (compare to emphysema which has marked hyperinflation). Clinical findings include wheezing, crackles, and cyanosis.

most common cause of food poisoning

Campylobacter infection. It is most often found in milk and poultry.

lack of vitamin D

Causes of hypovitaminosis D include lack of precursor molecules, or lack of activating enzymes. Lack of precursors: Lack of sunlight, fat malabsorption. Lack of enzymes: Liver failure, kidney failure, and alcoholism which induces CYP enzymes causing increased deactivation of vit D.

CLL

Chronic lymphocytic leukemia. Neoplastic proliferation of Naive B-cells which co-express CD-5 and CD-20 !!!!! (CD-5 is normally on a T-cell). Blood smear has increased lymphocytes with smudge cells on smear: (smudge cells occur as the leukemic cells are prone to mechanical disruption)

atherosclerosis complications

Consequences of atherosclerosis: - Hypertension (renal artery atherosclerosis may activate the renin-angiotensin-aldosterone system) - Aneurysms (weakening of vessel wall) - Ischemia from narrowing of medium size vessel (symptoms appear after *70% stenosis!!!!*) — e.g., peripheral vascular disease (popliteal) - ischemic heart disease (coronary artery) - ischemic bowel disease (i.e., mesenteric artery ischemia) Thrombosis — - MI (coronary artery) - stroke (Middle cerebral artery) - small bowel infarction

Acute Endometritis

Considerable presence of polymorphonuclear leukocytes in the endometrium. Most cases - ascending infection from the cervix. Abortion Delivery medical instrumentation.

where are lymphoid tissues often found??

Consist of dense accumulations of lymphocytes Located at: Sites that provide a possible route of entry of pathogens Sites that are liable to infections. Also, often found near epithelial lining (epithelium-associated lymphoid tissues). E.g. Mucosa-associated lymphoid tissue (MALT) or bronchus-associated lymphoid tissue (BALT). The tonsils or peyer's patches are examples of mucosa-associated lymphoid tissues.

Conus medullaris

Conus medullaris = end of the spinal cord. In adults, this is usually at the level of L1-L2.... L3 in neonates

Thrombin

Converts fibrinogen to fibrin monomers fibrin stabilizing factor (13) cross-links soluble fibrin monomers

Cytopathic-Cytoproliferative Inflammation

Cytopathic, cyto-proliferative inflammation Characteristic of viral mediated damage in absence of host inflammatory response. Examples include: - 1. Cellular inclusions 2. Multinucleation 3. Cell necrosis 4. Dysplasia

Explain the pharmacology of drugs used in the treatment of seizures

Decrease NA influx via fast Na+ channels: - carbamazepine, phenytonin facilitation of GABA mediated hyperpolarizations (benzos, barbituates) Decrease excitation effects of glutamate Decrease presynaptic Ca++ influx (ethosuxamide)

Respiratory acidosis

Decreased pH, Increased PCO2, increased bicarb (renal increase compensation) Common causes: hypoventilation due to ephysema, pulmonary edema

21 hydroxylase deficiency

Deficiency leads to: - ↓ Aldosterone - ↓ Cortisol - ↑ Androgens features: hyponatremia, hyperkalemia and hypovolemia due to lack of aldosterone life threatening hypotension due to lack of cortisol ambiguous genitalia or clitoral enlargement and labial fusion (females) or precocious puberty (males) due to excess androgens

Familial colorectal carcinoma: definition

Defined by two or more first-degree relatives with colorectal carcinoma

Pulmonary embolism tests

Definitive diagnosis is made with Pulmonary CT angiogram, which shows obstructed vessel - ECG - Echocardiogram -CXR - V/Q scan shows decreased perfusion with areas of normal ventilation

delirium vs dementia

Delirium- impaired consciousness with *inattention* - Acute onset, often reversible. - hallucinations likely to be visual Dementia- insidious onset, often progressive, irreversible. Disturbance of multiple higher cortical functions including memory, thinking, language, judgement. can be seen in Cortical (Alzheimers, dementia with Lewy bodies) or subcortical (Parkinsons, Huntingtons), disorders. also vascular (multi-infarct) or metabolic (hepatic failure) disorders.

Hepatitis D

Delta hepatitis is caused by the hepatitis D virus (HDV). This small single-stranded circular RNA delta virus. Transmission by blood, sexual.

Hypothyroidism derm, GI, Musculoskeletal

Dermatologic: - Coarse, brittle hair/nails - Yellow/orange skin - Myxedema (non-pitting edema due to interstitial accumulation of osmotically active mucopolysaccharides) of the hands, face, periorbital region. Gastrointestinal: - ↓ GI motility → constipation Musculoskeletal: - Carpal tunnel syndrome

Esophageal squamous carcinoma

Esophageal cancer: most common form worldwide is squamous cell carcinoma (90%)- malignant prolifferation of squamous cells. Usually arises in middle or upper 1/3s. These patients present initially with dysphagia (commonly to solids only, but may progress to liquids) & weight loss. Also *horse voice* if involves *recurrent laryngeal nerve*

Syndrome of inappropriate ADH secretions (SIADH)

Excessive ADH secretion - HYPOOnatremia and LOW serum osmolality (hold too much water) - Mental status changes, seizures

Cushings

Excessive cortisol, so muscle wasting (weakness, thin extremities) - Moon facies, buffalo hump, truncal obesity (excess glucose, so excess insulin, and fat stores in face, back, trunk), acne, hirsuitism. - abdominal striae (cortisol impairs collagen synthesis, so weak collagen leads to easy blood vessel rupture) - HTN (cortisol upregulated Alpha-1 receptors on arterioles to upregulate vascular tone - Osteoporosis, immune suppression

Thyroid hormone functions

For thyroid hormone functions, remember the 4 B's. Brain maturation Bone growth (but too much = resorption) Beta-adrenergic effects BMR ↑

Extrinsic receptor-ligand pathway (!)

FAS ligand binds FAS death receptor (CD95) on target cell. Ie, NEGATIVE selection for T-cells in thymus. Another example is TNF-receptor

Pyrexia of unknown origin (PUO)

FUO refers to a prolonged fever without an established etiology despite intensive evaluation and diagnostic testing.

nutmeg liver

Failure of adequate venous drainage from the liver leads to chronic passive congestion (congestive hepatomegaly), with blood backing up in centrilobular areas. This gives rise to a gross appearance picturesquely labelled "nutmeg liver". Microscopically, the nutmeg pattern results from congestion around the central veins This is usually due to a "right sided" heart failure.

Normal hemoglobin types

Fetal- (alpha 2, gamma 2) Hemoglobin A- (alpha 2, beta 2) Hemoglobin A2 (alpha 2, delta 2)

treat SLE

Fever, rash, MSK and serosi3s generally respond to treatment with o Hydroxychloroquine o NSAIDS o Low to moderate dose steroids as needed for acute flares cyclophosphamide- Used for immunosuppression in cases of serious SLE organ involvement, esp. severe CNS involvement, vasculitis and lupus nephritis

fibrocartilage

Fibrocartilage has characteristics intermediate between those of hyaline cartilage and dense connective tissue. Its presence indicates the need for resistance to compression and shear forces. Fibrocartilage contains type II collagen and also abundant type I collagen found in: - intervertebral discs - meniscus of knee No perichondrium

blood plasma vs serum

Fluid portion of blood, contains proteins. Albumin: maintains oncotic pressure of the blood. Clinical Correlate: Burn victims and patients with nephrotic syndrome lose albumin (through their skin and urine, respectively), resulting in edema due to loss of oncotic pressure. Gamma and beta globulins: transport hormones, metal ions, and lipids. Blood coagulation proteins, including fibrinogen → fibrin is the reaction that forms the fibrin clot. Plasma without fibrinogen is serum.

Aschoff bodies

Foci of swollen eosinophilic collagen lymphocytes Plasma cells Enlarged macrophages called Anitschkow cells

Thyroid gland anatomy

Functional anatomy of the thyroid gland consists of: - Follicles, composed of follicular cells - Colloid - Parafollicular cells

fusion inhibitors

Fusion inhibitors block gp41 conformational change → virions can't fuse w/ CD4 cells Enfuvirtide

investigate head injury

GCS CT MRI

ganglia

Ganglia are aggregations of neuron cell bodies outside of the CNS.

Explain the difference between genetic, phenotypic and legal sex.

Genetic: Chromosomal Sex: XX XY XXY Phenotypic: Sexual Characteristics Legal Sex: Birth Cert: Will say what you were born genetically. Can have a legal sex change.

Describe the difference between genotype and phenotype.

Genotype is an organism's full hereditary information - even if not expressed. • Represents it's exact genetic make up - particular set of genes it possesses. • If genes differ at even one locus (position in genome) --> different genotypes. • Genotype is a major influencing factor in the development of your phenotype but it's not the only one. Even 2 organisms with identical genotypes differ in their phenotypes (e.g. monozygous twins) - their mothers can tell them apart, different fingerprints. • Phenotype is an organism's actual observed properties - morphology, development, behavior.

Nephrotic syndrome (!!!)

Glomerular disorders with 1) Massive proteinuria (!!) 2) *Hypoalbuminemia*— 3) Generalized *pitting edema 4) Hyperlipidemia and hypercholesterolemia 5) *Hypogammaglobulinemia* 6) Hypercoagulable state

hyatiform mole appearance

Grape-like appearance (gross), proliferation of trophoblastic tissue, hydropic villi and absence of foetal vessels (Histology)

Hamartomatous Polyps

Hamartomatas are *benign* tumor-like masses of mature tissue *endogenous* to the site of their development. Hamartomatous polyposis syndromes are rare, but are composed of important intestinal and extra-intestinal manifestations. Hamartomatous polyps can occur sporadically or can be part of an acquired syndrome. The four main types of hamartomatous syndromes are: - Juvenile polyposis syndrome - Peutz-Jeghers syndrome - Cowden syndrome - Cronkhite-Canada syndrom

OA changes hand

Heberden's nodes- bony swellings that develop in the distal interphalangeal joints (DIP) . fusion of joints

3 types of cartilage

Hyaline Cartilage Elastic Cartilage Fibrous Cartilage

HTN and small vessel disease

Hyaline arteriolosclerosis and sclerosis (deposits of fibrinoid and acute necrosis of the vessel walls, esp in kidney)

Hydralazine

Hydralazine increases *cyclic guanosine monophosphate (cGMP)* levels, which *reduces* calcium release from the sarcoplasmic reticulum of smooth muscle, ultimately resulting in *smooth muscle relaxation*, and thus decreases BP. Since it dilates *arterioles* more than veins, there is good afterload reduction.

Hypertension

Hypertension: defined as *systolic greater than 140 mmHg* and/or *diastolic greater than 90 mmHg* The prevalence of HTN increases with age, smoking, alcohol, high salt diets, obesity, diabetes, and inactivity. HTN is more common in African Americans. and Native Americans Divided into *primary* and *secondary* hypertension: (note most cases are *primary*

manage anaphlaxis

IM adrenaline (raises BP, reduce swelling, smooth muscle relaxation) Hartmans BP anti-histamines (chlorphenamine) IV Hydrocortisone IV nebulized salbutamol for bronchospasm

intrinsic pathway vs extrinsic pathway clotting factors

INT= PTT (INT HEP PTT) 12, 11, 9, 8 EX= PT (EX WAR PT) 7

Herpes structure

Icosahedral capsid. Enveloped, linear dsDNA viruses. Very large. Envelope derived by budding from nuclear membrane (not cytoplasmic membrane) because assembly occurs in the nucleus.

Hep C structure

Icosahedral capsid—enveloped, linear, (+) sense ssRNA flavivirus - lipid-bilayer envelope containing two virus specific glycoproteins E1 and E2

peripheral tolerance

If an antigen is recognized in the peripheral tissues *without a costimulatory signal* then the lymphocyte undergoes *anergy* or *apoptosis* CD4+ T-cell uses its TCR to bind MCHII on the dendritic cell. Requires CD28 on T-cell to bind B7 on dendritic cell. Apoptosis here, the T-cell has CD95 (FAS)... regular binding of TCR to MHCII without second signal causes cell to express FAS-L... this binds to FAS and causes apoptosis. (can also apoptose other B or T cells)

tissue healing 3 r's

If the final appearance recapitulates normal structure, this is RECONSTITUTION. If the resulting tissue may be abnormal this is REGENERATION. Proliferation of the same type of cells . Require intact connective tissue scaffolding If there is scar formation (I.e. replacement by matrix and collagen), this is termed REPAIR.

secondary TB

If the primary infection isnʼt resolved, the inflammatory process may spread to other parts of the lung (apex, higher O2).

Type 2 collagen

In Cartilage, vitreous humor

Secondary hypertension

In about 5% of cases, the hypertension has an identifiable cause and this is known as secondary hypertension

nerve impules in myelated vs unmyelinated

In myelinated fibers propagate by saltation Along unmyelinated fibers, impulses move continuously as waves

Kupffer cells

In the luminal surface of the endothelial cells in sinusoids. They are *resident macrophages* of the liver. Function : Metabolise old erythrocytes Digest haemoglobin Secrete protein related to immunological processes Destroy bacteria

parietal cell acid secretion

In the parietal cell: 1) H+ generated by dissocion of water into H+ and OH-. 2) OH- to combine with CO2 to form HCO3- 3) HCO3- transported into the blood in exchange for chloride 4) H+ pumped into the gastric lumen in exchange for K+ Parietal cell has receptors for: 1) H2 2) M3) 3) gastrin

H-pylori in stomach and duodenum

In the stomach, chronic inflammation via H. pylori *disrupts the gastric mucosal barrier* as well as regulation of parietal cells, leading to *increased acid output*, causing ulceration in gastric mucosa. The exact mechanism by which H. pylori does so is not completely understood. Excess acid production can also lead to *duodenal mucosa metaplasia* into gastric mucosa (which H. pylori can then infect). Also *in the duodenum*, H.pylori induces an *inflammatory reaction that reduces bicarbonate* secretion by duodenal epithelial cells, *resulting in decreased duodenal mucus to buffer the caustic gastric acid*.

causes of cerebral edema

Inflammation of the brain (as in meningitis). Tumor Hemorrhage

SLE and heart

Involvement of heart on ALL 3 layers, endocarditis, myocarditis, pericarditis. Classic finding is *Libman-sacks endocarditis*. Key feature of endocarditis is vegetation on surface of heart values... usually they are on one surface of values, but Libman-Sacks are on BOTH sides of value.... They are deposition/inflammation of type 3 hypersensitivity

LH function

LH in the proliferative phase o (1) Increases the synthesis of 17-ketosteroids (KS) in the theca interna. (dehydroepiandrosterone (DHEA) and androstenedione.) o (2) DHEA is converted to androstenedione. synthesize testosterone for conversion by aromatase into estradiol o (3) An oxidoreductase converts androstenedione to testosterone. o (4) Testosterone enters granulosa cells and is aromatized to estradiol. 2. LH surge is induced by a sudden increase in estrogen. 3. LH in the secretory phase o Theca interna primarily synthesizes 17-hydroxyprogesterone (17-OH-progesterone).

Enoxaparin

LMWH (low molecular weight heparin) • Same mechanism, but preferentially inhibits Xa compared to IIa

Iso-osmotic dehydration

Loss of isotonic fluid from ECF - ECF volume decreases all else the same !! Examples, hemorrhage, diarrhea, burns, vomiting

M line-

M-line - band of connections between myosin filaments (mediated by proteins, e.g. myomesin)

Lung cancer

MOST common cause of cancer *mortality* (lung is #2 in *incidence* for both sexes behind breast/prostate, but lung cancer is highest mortality) ... key risk factors are cigarette smoke (*polycyclic aromatic hydrocarbons*) , radon (colorless, odorless gas... comes from *uranium* decay), and asbestos.

ITP- idiopathetic/immune thrombocytopenia purpura

MOST common cause of thrombocytopenia in both children and adults Type 2 hypersensitivity- autoimmune production of IgG autoantibodies against (fibrinogen) receptor GpIIb/IIIa on the platelet surface. The autoantibodies are PRODUCED by plasma cells in the spleen, they then coat the platelets, and then the splenic macrophages then destroy the coated platelets.

B12 deficiency symptoms

MUCH less common than folate deficiency. B12 deficiency causes neurological symptoms: -Loss of dorsal column function (↓ vibration and position sense) -Loss spinocerebellar tracts → ↓ proprioception -Demyelination of the lateral corticospinal tract → spasticity, weakness Neurological symptoms are due to demyelination of spinal cord. (called subacute degeneration of spinal cord)!!!! Very impt!!! Note: Megaloblastic anemia caused by B12 deficiency can be corrected by folate administration, but the neurological symptoms can not!!

causes of back pain

Mechanical: • Spinal disc herniation ("slipped disc") • Thoracic or lumbar spinal stenosis • Spondylolisthesis and other congenital abnormalities • Fractures Inflammatory: • Seronegative spondylarthritides (e.g. ankylosing spondylitis) • Rheumatoid arthritis • Infection - epidural abscess or osteomyelitis Neoplastic: • Bone tumors (primary or metastatic) Metabolic: • Osteoporotic fractures • Osteomalacia Psychosomatic • Paget's disease Referred pain: • Prostate Cancer • Posture • Depression

Warfarin

Mechanism: Inhibits vitamin K-dependent γ-carboxylation of factors X, IX, VII, II ("1972"), protein C, and protein S • Warfarin's inhibition of γ-carboxylase is irreversible → effects last 7-10 days after stopping therapy. • Follow PT or INR (normalized version of PT)

Membranous glomerulonephritis

Membranous glomerulonephritis is an immunologically mediated disease in which deposits of mainly IgG and complement collect in the basement membrane and appear in a diffuse granular pattern.

Hypothyroidism metabolic consequences

Metabolic: - ↓ BMR (basal metabolic rate); ↓ O2 consumption → ↓ RR - Positive nitrogen balance (anabolic) → weight gain - ↓ Heat production → ↓ sweating and cold intolerance - Growth retardation

Biguanides:

Metformin is the important biguanide and the FIRST LINE agent for DM type II. Mechanism: Metformin activates AMPK (AMP-activated protein kinase) → ↑ expression of orphan nuclear receptor SHP (small heterodimer partner) → inhibits expression of liver PEPCK and glucose-6-phosphatase, thus repressing hepatic gluconeogenesis. It also increases peripheral insulin sensitivity and utilization of glucose.

Anemia of chronic disease and causes

Microcytic. occurs in the setting of a chronic infectious or inflammatory process (or cancer). It is one of the most common causes of anemia in hospitalized patients. Common causes include: - Chronic infectious processes (TB, osteomyelitis, lung abscess) - Malignancy (breast, lung, Hodgkin's lymphoma) - Autoimmune disease (SLE, RA)

name two media are used to grow MTB

Middlebrook's medium which is an agar based medium Lowenstein-Jensen medium which is an egg based medium.

Rheumatic heart valves

Mitral valve is most often affected with rheumatic heart disease, followed by mitral and aortic together, then aortic alone, then mitral, aortic, and tricuspid together.

duodenal ulcers

Most ulcers (90%) involve the *proximal duodenum* (aka *duodenal bulb*) Almost always due to H-pylori, but rarely *may* be due to *ZE-syndrome* (Zollinger Ellison). Presents with epigastric pain which will generally *improve during a meal* (think "all acid is in stomach") and *cause pain hours after a meal*.

causes of proximal muscle weakness

Myasthenia gravis MS Cushing's syndrome lumber stenosis malignant disease

TB

Mycobacterium tuberculosis (TB, tubercles bacillus) is an acid-fast (shows up red on Ziehl-Neelsen stain), obligate aerobic rod. transmitted by aerosolized respiratory droplets.

myelin resistance

Myelin increases resistance across the cell membrane and decreases capacitance.

Hematopoetic stem cell divides into: (acute leukemia)

Myeloid progenitor (>20% is Acute Myeloid Leukemia (AML!!!) Lymphoblasts (>20% is acute lymphoblastic leukemia (ALL )

Diffuse Proliferative Lupus nephritis- ClassIV

One complete glomerulus and part of another one are seen. Note the mesangial and capillary wall deposits of IgG.

Non-enzymatic glycosylation

NEG in large/medium vessels, leads to atherosclerosis (and its complications) NEG in small vessels leads to hyaline arteriolosclerosis ('pink' material in wall of small blood vessels decreasing lumer.....classically occurs kidney) NEG of hemoglobin leads to HbA1c, which is a marker of glycemic control.

NRDS seen in which conditions

NRDS is most commonly seen in infants who are: - Preterm - C-section delivery (vaginal birth is a MAJOR STRESS which results in increase cortisol) - Infants of diabetic mothers (baby produces too much insulin which *inhibits* surfactant).

NSAIDs and gastric ulcers

NSAIDs are the second most important cause of PUD. NSAIDs decrease prostaglandin production in GI tract, which leads to decreased bicarbonate and mucus production. Less bicarbonate and mucus makes gastric epithelial cells more vulnerable to the damage of gastric acid.

Sodium channel blockers

Na channel blockers (block luminal Na channels in the *distal renal tubule* → ↓ reuptake of Na → ↓ efflux of K into the urine) — e.g., triamterene, amiloride Note: *normally*, to maintain ionic charge balance, *influx of Na* from the *distal tubule lumen* into the *principal cells* leads to *efflux of K* from the *principal cells*, where K+ then goes into the urine in the distal tubule lumen*. Thus, blocking the luminal Na channels in the distal tubule prevents efflux of K into the urine, thereby retaining the K+ in the body.

Nasal Polyposis

Nasal polyposis results from chronic inflammation of the nasal and sinus mucous membranes. Chronic inflammation causes a reactive hyperplasia of the intranasal mucosal membrane, which results in the formation of polyps. Seen in: asthma - CF - allergic rhinitis

causes of growth retardation

Neglect, poor socioeconomic setting, poor sucking. Prematurity with complications, chronosomal abnormalities, chronic disease (CF), malsbsorption (Crohn's), hyperthyroidism.

In-Situ Carcinoma

Neoplastic cells have not invaded basement membrane, there is a high nuclear/cytoplasmic ratio and clumped chromatin, neoplastic cells encompass entire thickness, and tumor cells are monoclonal.

Lymphoma

Neoplastic prolifferation of lymphoid cells which forms a MASS. May arise in - lymph node (Non Hodgkin Lymphoma (60%)) or extra-nodal tissue. (Hodgkin Lymphoma (40%)

neutrophil destruction of phagocytosed material

Neutrophils form phagosome, joins lysosome to form phagolysosome. Destruction of phagocytosed material occurs in 2 days: 1) O2 dependent killing (most effective) 2) O2 independent killing

neutrophil Resolution

Neutrophils undergo apoptosis (!!), disappear within 24 hours after resolution, become pus.

HIV drugs

Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Nucleoside reverse transcriptase inhibitors (NRTIs). Protease inhibitors (PIs). Fusion inhibitors. CCR5 antagonists . Integrase inhibitors.

AML onset

Older adults, 50-65.

Greenstick fracture

One side of bone is broken, other 'bends'... occurs in children

Immunized

Only anti HBs (anti-HBV surface antibody)

treat glaucoma

Open angle: first line treatments are medications including beta-blockers (e.g. Timolol) or carbonic anhydrase inhibitors (e.g. acetazolamide) to decrease aqueous humor production. prostaglandin analogues (e.g. latanoprost) to promote aqueous humor drainage.

metabolic backpain

Osteomalacia, Paget's disease

Tunica adventitia/externa:

Outermost connective tissue layer consisting of fibroblasts, type I collagen and elastic fibers. In large arteries., the tunica adventitia contains the *vasa vasorum*. Structures of the adventitia are *longitudinally oriented.*

female puberty changes

Ovaries • Begin to increase in size • Follicle growth and development (including steroidogenesis) is dependent on gonadotrophins. Breasts • Start to enlarge • Initiation of breast development = thelarche - 1st physical outward indication of the commencement of puberty pelvis widens

schizophrenia brain losses

PET scan showed Dramatic reductions in the profiles of the gray matter were detected Region of greatest loss : The temporal and frontal brain regions that control memory, hearing, motor functions, and attention.

4 types of thyroid carcinomas (!!)

Papillary, follicular, medullary, and anaplastic.

Types of buffers

Phosphates: Intracellular protein, Hb, organic and inorganic phosphates. Bone releases calcium to buffer, forms CaHPO4.

HIV opportunistic infections

Pneumocystis jirovecii - esophageal Candidiasis - CMV - toxoplasmosis

kidney podocytes

Podocytes (or visceral epithelial cells ) are cells of the visceral epithelium in the kidneys, they possess an important role in glomerular filtration and act as a barrier to macromolecules.

polymorphism

Polymorphism is when two or more clearly different phenotypes exist in the same population of a species—in other words, the occurrence of more than one form or morph. In order to be classified as such, morphs must occupy the same habitat at the same time and belong to a population with random mating. (Ie, Jaguar animals with different fur colors from wikipedia)

What variables determine the likelihood of malignant change in a polyp?

Polyp size Cancer is rare in tubular adenomas less than 1 cm in diameter Histologic architecture high risk (50%) in sessile villous adenomas that are greater than 4 cm in diameter. Severity of dysplasia. Severe dysplasia is likely to progress to cancer. Found typically in villous areas. Of all these, size is the most important factor.

where does postive and negative selection for T-cells occur?

Positive in the *cortex* Negative in the *medulla* of the thymus

Complications HCV

Postnectoric cirrhosis, hepatocellular carcinoma - Membranoproliferative glomerulonephritis - B cell lymphoma

The three main classifications of disc herniation are :

Protrusion (contained herniation or sub-ligamentous herniation) Extrusion (non-contained herniation, or trans-ligamentous herniation) Sequestration (free fragment).

Nasal polyps

Protrusion of edematous, inflamed nasal mucosa, usually secondary to repeated bouts of rhinitis. Often develops with *cystic fibrosis* !! in children. Also develops in aspirin intolerant asthma.

deep venous thrombi

Pulmonary embolism Pain and swelling of the limb. Venous gangrene or limb loss. Recurrent pulmonary embolism → pulmonary hypertension

quadrouple therapy

Quadruple therapy is used in regions with clarithromycin-resistant H. pylori. It includes a proton pump inhibitor (PPI), bismuth, and two antibiotics.

RANK

RANK is a membrane protein found on surface of *osteoclasts* (RANKL) Is a member of the tumour necrosis factor TNF) cytokine family, found on *osteoblasts* Functions as a key factor for osteoclast differentiation and activation

Grey hepatatation

RBCs broken down and lung turns grey.

colonic polyps

Raised protrusions of colonic mucosa. Can be neoplastic (aka adenomatous.) or non-neoplastic.

Insulin Type 1 IDDM meds

Rapid Acting: Insulin glulisine, insulin aspart, and insulin lispro (GAL). Short acting: Regular, and Semilente Intermediate acting: Lente, Isophane (NPH) Long acting: Ultralente (Insulin glargine, insulin detemir, Protamine-zinc)

Clinical presentation of Hepatitis B

Recovery in >90% of immunocompetent patients. 1-2% develop chronic hepatitis. So Acute hepatitis, MAY (but unlikely) progress to chronic Newborns and immunodeficient patients more likely to develop chronic hepatitis (>90% of cases)

fiber and colon cancer

Reduced fiber content leads to decreased stool bulk. Increased feacal transit time in the bowel. Altered bacterial flora of the intestine. High cholesterol intake in red meat enhances the synthesis of bile acids by the liver . Less of vitamins A, C, and E (in refined diets) which may act as anti-oxidants.

Reed Sternberg cells

Reed-Sternberg cells are large B-cell origin, binucleate with prominent "owl eyes" nucleoli .....(NO CD20+ !!!!!) May lead to fibrosis!!

Aortic regurgitation overview

Regurgitation of ejected blood from the aorta back into the left ventricle during *early diastole*! (...leads to↓ peripheral arterial *diastolic BP*) Also, this ↑ LVEDV (left ventricular end-diastolic volume) → Frank-Starling mechanism causes *increase in stroke volume* during *systole*, causing *↑ systolic BP*) → wide *pulse pressure* (systolic-diastolic). This above phenomenon leads to concept called *hyperdynamic circulation*, and shown with bounding pulses, plusing nail bed, and head bobbing.

Intrarenal AKI

Renal azotemia (intrarenal AKI): kidneys are damaged → impaired glomerular filtration and/or renal tubular function → abnormally high levels of nitrogen containing compounds such as BUN and creatinine.

Long term BP regulation

Renin-Angiotensin-Aldosterone System: Long-Term Regulation of Blood Pressure Decreased BP activates the RAAS. Renin is secreted by the kidneys and increases conversion of angiotensinogen to angiotensin, which causes increased release of aldosterone from the adrenal cortex , decreased Na + and water excretion, resulting in increased extracellular fluid volume and BP.

Chronic rheumatic fever

Repeat exposure to *group A β-hemolytic streptococcal* causes relapse in acute phase.... and each relapse increases risk for *chronic rheumatic valvular disease* Chronic rheumatic valvular disease results in scarring of the valves (*mitral > aortic >> tricuspid*)... This scarring causes *stenosis*, most always in mitral valve, which leads to thickening of the chordae tendineae and cusps. If scarring of the aortic valve, leads to *fusion of the commissures*.!! ( Damaged valves can cause *endocarditis*.

Restrictive lung diseases

Restricted *filling* of the lung. ↓ pulmonary compliance ↑ lung elasticity ↓ lung volumes Because *all lung volumes* are reduced (especially FVC), the ratio of FEV1/FVC >80%.

Subdural hematoma

Rupture of the Bridging veins. They are most common in the very young (thin-walled vessels) and the elderly. Crescent shaped hematoma, less dense due to dilution with CSF. Indicative of high acceleration/deceleration injury with tearing of bridging veins or cortical arterioles. Most common over the lateral aspects of the cerebral hemispheres.

4 encapsulated bacteria spleen

S. pneumoniae, N. meningitidis, H. influenzae, Klebsiella pnemoniae

Hypo-osmotic over hydration

SI-ADH, or drink a lot of water. ECF volume increases, ECF osmolarity decreases. There is a fluid shift ECF--> ICF So ICF volume increases, ICF osmolarity decreases

Schizophrenia DSM

Schizophrenia is a group of psychotic disorders characterized by 2 of following for 1 month period: (usually > 6 months) - delusions - hallucinations - negative symptoms (inability to speak, initiate and persist in activities) - major social/occupational dysfunction below the level prior to symptom onset - not due to a substance

sciatica

Sciatica is radicular pain in the L5 or S1 distribution. Pain in: Deep buttock Posterior or posterolateral thigh May extend below the knee, into the lower leg and lateral foot. Described as shooting or stabbing. Sometimes paresthesias in the same distribution. Aggravated by coughing, sneezing, or straining

Describe presentations of neonatal emergencies

Sepsis • Neonatal sepsis is almost always acquired from the mother, even if there has been a caesarean. Respiratory Distress Syndrome • Respiratory distress syndrome (RDS) is a collection of signs and radiologic features - cyanosis, recession, tachypnoea, apnoeas with progressive hypoxaemia and hypercarbia. • The cause is lung immaturity is most often surfactant deficiency. Meconium Asiration • Particularly common if the fetus is asphyxiated - causes it to pass meconium and gasp. • If meconium is inhaled it leads to mechanical obstruction of the small airways and alveoli.

primary vs secondary hyperthyroidism

Serum TSH varies based on etiology: - Primary hyperthyroidism: ↓ TSH - Secondary hyperthyroidism: ↑ TSH. In the rare case that a patient has secondary hyperthyroidism due to a TSH-secreting pituitary adenoma → inject TRH and look for ↑ in TSH - Note: When hyperthyroidism is clinically suspected, serum TSH is usually the most sensitive test.

endometrial polyps

Sessile masses that project into the endometrial cavity. Single or multiple and are usually 0.5 to 3 cm in diameter but occasionally large and pedunculated. Asymptomatic or may cause abnormal bleeding. Two histologic types: Functional endometrium, Hyperplastic endometrium (more commonly), mostly of the cystic variety. Rare association with adenocarcinomas Observed in association with the administration of tamoxifen.

Clinical features of MI

Severe, crushing chest pain > 20 mins!! radiates to left arm/jaw -Dyspnea - Diaphoresis Symptoms *NOT* relieved by nitroglycerin

Kidney in SLE

Some anti-dsDNA antibodies cross-react with the glomerular basement membrane. • autoantibodies may form intravascular immune complexes, which are deposited in glomeruli. - autoantibodies may bind to antigens already located in the glomerular basement membrane, forming immune complexes in situ. • Immune complexes promote an inflammatory response by activating complement and attracting inflammatory cells, including lymphocytes, macrophages, and neutrophils.

Gestational Trophoblastic disease

Spectrum of tumour or Tumour-like conditions of progressive malignant potential characterized by proliferation of trophoblatic tissue.

Stable angina

Stable angina is chest pain *precipitated by exertion* (e.g., walking uphill) where *oxygen demand exceeds oxygen supply* and is *relieved* by *rest* (decrease demand) or the administration of *nitrates* (vasodilates both arteries and more so, *veins) Note, *stable angina* leads to *reversible* injury to myocytes (*cellular swelling!!) ..... BUT Coronary artery disease (CAD) is often progressive, thus patients with stable angina pectoris often develop unstable angina and/or sustain myocardial infarction (MI).

choriocarcinoma stages

Stage Stage I - Confined to the uterus Stage II - Limited to the genital structures Stage III - Lung metastases Stage IV - Other metastases + Prognostic factors can be added to the stage (WHO) Chemotherapy for gestational choriocarcinoma -Very good results up to 100% cure or remission in all patients (except some who had high-risk metastatic trophoblastic disease).

liver functions

Storage of glycogen, buffer for blood glucose. Amino acid, protein and ammonia metabolism Metabolism of cholesterol and fat. synthesis of many plasma proteins, including: Clotting factors Growth factors Fibrinolysis proteins Complement involved in formation of calcidiol in Vitamin D detoxification of drugs/poisons

bone subchondral infarcts vs bone medullary infarcts

Subchondral infarcts Chronic pain - Pain is initially associated only with physical activity but then becomes progressively more constant as secondary changes supervene. Subchondral infarcts, often collapse and may predispose to severe, secondary osteoarthritis. Medullary infarcts are clinically silent (usually remain stable over time and rarely are the site of malignant transformation.)

Granulocytes

Subclass of leukocytes; includes: basophils, neutrophils, and eosinophils

left cerebral hemisphere edema

Swelling of the left cerebral hemisphere has produced a shift with herniation of the uncus of the hippocampus through the tentorium. Note: any acute cerebral swelling can often produce herniation of the cerebelllar tonsils into the foramen magnum

Systolic murmurs

Systolic murmurs: 1) Aortic/Pulmonic Stenosis 2) Mitral/Tricuspid Regurgitation 3) Mitral Valve Prolapse 4) Ventricular Septal Defect Think "sten-O-sis": problem with valve Opening. murmurs secondary to stenosis occur when the involved valve is opening (i.e. aortic valve opens in systole, thus aortic stenosis is a systolic murmur)

Laplace equation, use it to predict effect of dilation of cardiac failure on tension in walls as it contracts

T = ( P * R ) / M Where T is the tension in the walls, P is the pressure difference across the wall, R is the radius of the cylinder, and M is the thickness of the wall An example of LaPlace Law is Dilated cardiomyopathy. In this condition heart becomes greatly distended and the radius (R) of ventricle increases. Therefore to create the same pressure (P) during ejection of the blood much larger wall tention (T) has be developed by the cardiac muscle. Thus dilated heart requires more energy to pump the same amount of blood as compared to the heart of normal size.

T-ALL

T-ALL: -Presents commonly as anterior mediastinal mass (thymus), also commonly in teenagers -Surface marker: CD1, CD2, CD3, CD4, CD7 (CD10 is a B-cell specific marker, so it is not present!!!). Note: it is also considered to be a LYMPHOMA because it is a thymic MASS, not a leukemia.... leukemia means floating around in blood).

TE fistula

TEF: abnormal connection (fistula) between trachea and esophagus, commonly congenital. What happens is we have a proximal esophagus which is *atretic* (ends in a blind pouch).... with a fistula conntecting trachea and *distal esophagus*

Fracture assessment/treatment

Take hx (allergies, medication, past medical, events of fracture) Try closed reduction first maybe, (apply traction to long axis of limb and reverse mechanism which produced fracture), except when: - Cannot cast (ie, hip) - Open, or non-union - potential for improves function Maintain reduction by external (casts, splints,etc) or internal (screws, rods, plates) stabilization.

Anemia

Technically defined as reduction in circulating RBC mass. Hb, Hct, and RBC count used as surrogate markers for RBC mass. Prevent with s:sx of hypoxia: - Weakness, fatigue, dynpnea: - pale conjunctiva and skin - headache/lightheaded - angina, especially w/ preexisting CVD Hb < 13.5g/dl in males: Hb < 12.5g/dl in females

spinal ganglia

The "capsule" encircling each of the neurons consists of : An inner portion with flattened satellite cells An outer portion of fibroblasts and fibrocytes, which have dark elongated small nuclei.

Zone 3 liver

The centrilobular zone III has the poorest oxygenation and is more sensitive to ischemic injury Zone III cells are more important for glycolysis, lipogenesis and cytochrome P-450-based drug detoxification (ie, alcohol, acetominophen)

The four major causes of intestinal obstruction are:

The four major causes of intestinal obstruction are: Herniation of a segment in the umbilical or inguinal regions Adhesion between loops of intestine Volvulus Intussusception

3 parts of a neuron

Three parts: 1) Dendrites Receive stimuli Multiple branched processes 2) Axon Integration and conduction of impulses Terminal arborization End bulbs (Boutons) which interact with neurons and non neuronal cells 3) Soma or cell body)

CF tests

chloride sweat test (two of them) - heel prick test - An abnormal nasal potential difference test. This test uses electrodes on the lining of the nose to see how well salts flow into and out of cells.

Meconium

The meconium sometimes becomes thickened and congested in the ileum, a condition known as meconium ileus. Meconium ileus is often the first sign of cystic fibrosis

Kidney medulla blood supply

The medulla does not have its own arterial blood supply but is dependent on the blood emanating from the glomerular efferent arterioles. Capillary loops in the medulla has a low level of oxygenation so, minor interference with the blood supply of the medulla may result in medullary necrosis from ischemia.

submucosa

The submucosa consists of areolar connective tissue that binds the mucosa to the muscularis. It contains many blood and lymphatic vessels that receive absorbed food molecules. Also located in the submucosa is an extensive network of neurons known as the submucosal plexus

Thiazide

The thiazides and related compounds are safe, orally active, but relatively weak diuretics. They control hypertension in part by inhibiting reabsorption of sodium (Na+) and chloride (Cl−) ions from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive Na+-Cl− symporter. Excretion of Cl −, Na + and accompanying H2O is increased. The increased Na + load in the distal tubule stimulates Na + exchange with K+ and H+ , increasing their excretion and causing hypokalaemia and a metabolic alkalosis. Some diuretics are 'potassium sparing' (bottom right). They are weak when used alone, but they cause potassium retention, and are often given with thiazides or loop diuretics to prevent hypokalaemia.

Myelin

The thickness of the myelin sheath is directly proportional to the diameter of the axon, and the larger the axon diameter, the longer is the internodal distance MPZ is a transmembrane protein, which functions in the compaction of apposing lipid bilayers of myelin.

puerperium

The time from the delivery of the placenta through the first few weeks after delivery. • Pelvic organs return to pre-pregnant state • Reversal of physiological adaptations to pregnancy • Establishment of lactation • Usually considered to be six weeks

Upper esophageal sphincter vs lower esophageal sphincter

The upper esophageal sphincter regulates the movement of food from the pharynx into the esophagus; the lower esophageal sphincter regulates the movement of food from the esophagus into the stomach.

androgens/estrogens and bone

These hormones are responsible for increased osteoblast activity and synthesis of bone extracellular matrix and the sudden "growth spurt" that occurs during the teenage years. Estrogens also promote changes in the skeleton that are typical of females, such as widening of the pelvis. Ultimately sex hormones, especially estrogens in both sexes, shut down growth at epiphyseal (growth) plates, causing elongation of the bones to cease. Lengthwise growth of bones typically ends earlier in females than in males due to their higher levels of estrogens. One way that estrogens slow resorption is by promoting apoptosis (programmed death) of osteoclasts.

Trypsin

Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine.

Thyroglossal duct cyst

Thyroid develops base of tongue, travels along thyroglssal duck to anterior neck. Normally it should involute, but if it persists, you get cystic dilation of the duct. Presents as ANTERIOR neck mass.

thyroid follicles

Thyroid follicles: formed by cells that synthesize, store and secrete thyroid hormone. Organic iodine in the diet is absorbed from the GI tract and an iodine pump in the follicle cells trap iodine within the thyroid gland.

Inspiratory capacity

Tidal volume + inspiratory reserve volume

Warfarin toxicity and reversal

Toxicity: initial paradoxical thrombosis, bleeding, skin/tissue necrosis Reversal: FFP (fresh frozen plasma; contains coagulation factors), vitamin K

Anaplastic carcinoma

Undifferentiated malignant tumor of thyroid, usually in elderly (over 65). -< 5% of overall thyroid cancer cases - Terrible prognosis. Can invade local structures and lead to respiratory compromise, dysphagia. highly malignant cells, 'undifferentiated'

Unstable angina

Unstable angina pectoris is described as chest pain *increasing in severity, frequency, and duration* that *occurs at rest* or that is *not relieved* by the administration of *nitrates*. Unstable angina pectoris is also known as *crescendo angina pectoris* and *pre-infarction angina pectoris*. Unstable angina pectoris episodes are triggered by situations in which there is an *acute plaque rupture * that leads to an *acute thrombosis* with *mural (non-occlusive) thrombus* formation. Typically a 90% decrease in corinary artery luminal area is necessary to cause unstable angina pectoris.... but note, this injury is *still reversible*

esophageal carcinoma cancer spread

Upper 1/3- cervical nodes Middle 1/3- mediastinal or tracheobronchial nodes Lower 1/3: celiac and gastric nodes

Neutrophils

Very phagocytic, no APC function.

HSV-1

Vesicles that rupture resulting in shallow, painful, red ulcers. HSV-1: transmission via respiratory secretions & saliva HSV-1 usually causes infection above the waist — for example: - *herpes labialis* — oral lesions, "cold sores" - *temporal lobe encephalitis* — most common cause of *sporadic encephalitis* in US Although HSV-1 infection typically occurs above the waist (e.g., herpes labialis), HSV-1 infection below the waist (e.g., herpes genitalis) sometimes occurs, possibly due to oral sex practices After primary infection, virus remains latent in *sensory ganglia (e.g., trigeminal ganglion*!!) and can reactivate in response to some *stressor or immunocompromise*. From cranial nerve ganglia, HSV may also *continue on to the brain → temporal lobe encephalitis*

why do t-cells die in HIV

Viral replication with subsequent cell lysis Progressive destruction of the of the lymphoid organ's architecture Persistent activation of uninfected cells (responding to opportunistic infections) leading to activation induced cell death.

protease inhibitors

Virally encoded protease cleaves polyproteins into mature proteins Protease inhibitors (-navir): saquinavir, ritonavir, indinavir

Pleura

Visceral pleura covers lung... attaches to chest wall where it is *parietal pleura*... in between is *pleural cavity*

Mitral valve prolapse murmur

a *midsystolic* or late systolic *click* and a mid-to-late systolic murmur is heard.

Leiomyomata

a benign smooth muscle neoplasm that is very rarely (0.1%) premalignant. They can occur in any organ, but the most common forms occur in the uterus, small bowel and the esophagus. Uterine fibroids are leiomyomata of the uterine smooth muscle. As other leiomyomata, they are benign, but may lead to excessive menstrual bleeding (menorrhagia), often cause anemia and may lead to infertility.

Stress fracture

a bone may fracture without visibly breaking. A stress fracture is a series of microscopic fissures in bone that forms without any evidence of injury to other tissues. In healthy adults, stress fractures result from repeated, strenuous activities such as running. Stress fractures are quite painful and also result from disease processes that disrupt normal bone calcification, such as osteoporosis. About 25% of stress fractures involve the tibia. Although standard x-ray images often fail to reveal the presence of stress fractures, they show up clearly in a bone scan

Tension PTX

a life threatening condition that develops differently than spontaneous PTX Tension PTX occurs when the visceral pleura or parietal pleura are involved and the resultant tissue defect forms a *one-way valve* that *lets air into the pleural space but NOT OUT* → trapping air in the pleural cavity. Positive pressure → displaces mediastinal structures and can compress the vena cavae causing ↓ venous return. This is typically manifested as a mediastinum that is *shifted to the contralateral side*. Additionally, because of the compression of the SVC and IVC, hemodynamic compromise is also seen (hypotension, tachycardia). Tension PTX presenting with signs of hemodynamic compromise must be treated with *immediate needle thoracostomy.*

CCR5

a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. This is the process by which T cells are attracted to specific tissue and organ targets. Many forms of HIV, the virus that causes AIDS, initially use CCR5 to enter and infect host cells. A few individuals carry a mutation in the CCR5 gene, protecting them against these strains of HIV.

Hereditary angioedema

a rare, autosomal dominantly inherited blood disorder that causes episodic attacks of swelling that may affect the face, extremities, genitals, gastrointestinal tract and upper airways HAE type I primarily caused because of abnormally low concentration and reduced function (mutation) of C1 esterase inhibitor, thus allowing proinflammation. May cause fatal asphyxiation.

Serosa/adventitia

a serous membrane composed of areolar connective tissue and simple squamous epithelium

Hyaluonic acid

a ubiquitous carbohydrate polymer that is part of the extracellular matrix. Hyaluronan is an important component of articular cartilage, where it is present as a coat around each cell (chondrocyte). When aggrecan monomers bind to hyaluronan in the presence of link protein , large, highly negatively charged aggregates form. These aggregates imbibe water and are responsible for the resilience of cartilage .

Drugs used to treat heart failure

a) diuretics b) ACE inhibitors c) ARBs d) cardiac glycosides e) β-blockers f) vasodilators

I band-

actin filaments During muscular contraction, the region of the I band will shrink

Entecavir-

abbreviated ETV, is an oral antiviral drug used in the treatment of hepatitis B infection. . Entecavir is a nucleoside analog, (more specifically, a guanosine analogue) that inhibits reverse transcription, DNA replication and transcription in the viral replication process. The drug's manufacturer claims that entecavir is more efficacious than previous agents used to treat hepatitis B (lamivudine and adefovir).

fistulas

abnormal connection or passageway between two epithelium-lined organs or vessels. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.

Mast cells activated by

activated by 3 things: 1) Tissue trauma 2) Complement C3a and C5a 3) Cross linking of cell surface IgE by antigen Immediate response of activation is release of preformed histamine granules, which mediates vasodilation of arterioles and increased vascular permeability (post capillary venule) Delayed response is production of AA metabolites, particularly leuoktrienes which maintain acute response (!!!)

Iso-osmotic overhydration

administer large volumes of Isotonic NaCl solution ECF only increases

Celiac disease presentation

adult celiac disease is often associated with anemia (due to iron deficiency and, less commonly, B12 and folate deficiency), diarrhea, bloating, and fatigue. Pediatric celiac disease, may manifest with classic symptoms, typically between the ages of 6 and 24 months (after introduction of gluten to the diet) with irritability, abdominal distention, anorexia, diarrhea, failure to thrive, weight loss, or muscle wasting - dermatitis herpetiformis (small, LOOKS LIKE herpes) due to IgA deposition at dermal papillae.

essential HTN causes

affecting cardiac output, peripheral resistance, or both. ie Gene defects in enzymes involved in aldosterone metabolism Mutations in proteins that affect sodium reabsorption

c4-c5 herniation

affects C5 nerve root and dermatome.... affects deltoid and there is abduction weakness. Decreased biceps jerk.

L3-L4 herniation

affects L4 nerve root and dermatome, medial surface of leg... affects quads, knee extension, knee jerk reflex

hypercoagulable state

aka thrombophilia!! balance between pro and anti-coagulant proteins is offset, may be inherited (primary) or acquired (secondary) classic presentation is recurrent DVT's or DVT's at young age, other sites include hepatic and cerebral veins examples: - lack of protein C or protein S - Also: -, factor V Leiden mutation (most common hereditary cause) - lack of anti-thrombin III - anti-phospholipid syndrome -mutant prothrombin - elevated homocysteine

risk factors for GERD and lifestyle modifications

alcohol, tobacco, obesity, high fat diet, caffeine, hiatal hernia. lifestyle modifications: Decrease intake of foods that reduce LES tone/pressure: ↓ Fat intake ↓ Alcohol intake ↓ Chocolate

reserve capacity aging

all organs have a 'reserve capacity' available to deal with high demand/stress. With aging, this is reduced. 1. Most adults are slower. 2. impact of stress is greater. 3. difficulty maintaining homeostasis (blood pressure, blood gases, acid/base balance) 4. pacing during tasks.

asterixis

also called the flapping tremor, is a tremor of the hand when the wrist is extended due to hepatic dysfunction which produces neurotoxic substances.

Neonatal respiratory distress

also known as *hyaline membrane disease* is the most common cause of respiratory distress in the newborn. The incidence of NRDS is *inversely proportional to gestational age*. Infants born *<28 weeks* have a 60% likelihood of development. NRDS is due to a *deficiency of pulmonary surfactant* from *type 2 pneumocytes* most commonly stemming from immaturity of the neonatal lungs. A deficiency in surfactant causes *↑ surface tension* in the alveoli and *wide scale atelectasis and decreased lung* compliance with each successive breath. Progressive atelectasis and decreased compliance → *protein-rich exudate* in alveoli, necrotic debris, and the formation of hyaline membranes, which can be found from the respiratory bronchioles to the alveoli. Surfactant production by *type II pneumocytes* is *greatly increased after the 35th gestational week*, thus the inverse correlation between NRDS and gestational age.

Pyelonephritis

an *upper* UTI, (pyelo="pelvis"), so it is *infection of the kidney* 1) *Ascending infection* *Vesicoureteral reflux* means incompetent vesicoureteral orifice (b/w *ureter and bladder*) → urine refluxes into ureters when bladder is under pressure → bacteria can ascend *from the bladder through the ureter to the kidney* 2) Hematogenous dissemination to the kidney (e.g., tuberculosis, staph) Presents with fever- - flank pain (sensitizes nerves of kidney) - leukocytos *with* WBC casts (as infection ascents tubule, they cast in shape of the tubule) - E. coli accounts for about 85% of community-acquired UTIs and 50% of hospital-acquired UTIs.

Celiac disease overview

an intestinal immune reaction to gluten. Gluten is digested by luminal and brush border enzymes into a *gliadin peptide*. Gliadin is deamidated by *tissue transglutaminase (tTG)* and is then able to interact with *HLA-DQ2* (95% of cases) or *HLA-DQ8* on APCs and be presented to *CD4+ T cells*. These T cells produce cytokines that are likely to contribute to the tissue damage and characteristic mucosal histopathology. A characteristic B cell response follows: this includes production of *anti-tissue transglutaminase, anti-deamidated gliadin*.

HBeAg

another antigenic determinent in HBV core. It indicated viral replication, thus high transmissibility.

Myasthenia gravis overview

anti-ACh (acetylcholine) receptor antibodies prevent ACh from binding postsynaptic ACh receptors and also induce the downregulation of postsynaptic ACh receptors → paresis (muscle weakness), paralysis

Antiphospholipid antibodies in SLE

antibodies against proteins when the proteins are bound to phospholipids, because when the protein is bound to the phospholipid the epitope is revealed. 3 tested: 1) anti-cardiolipin 2) Lupus anticoagulant 3) Anti- B2- glycoprotein I

Anti- HBc

antibody to HBcAg. IgM means accute infection IgG means chronic infection or prior exposure Positive during the window.

Type 2 HS

antibody-mediated) hypersensitivity reactions): IgM and/or IgG autoantibodies bind fixed antigens in specific tissues—ie, there are *no circulating immune complexes* type 2 HSRs are usually tissue-specific instead of systemic (vs. type 3 HSRs which involve circulating immune complexes and are ∴ usually systemic) • 2 categories of pathogenesis in type 2 HSRs: • 1) Cytotoxic: antibodies can bind and initiate cytotoxicity via a variety of mechanisms, including: - Opsonization and phagocytosis - Complement-mediated inflammation and tissue damage - Fc receptor-mediated inflammation and tissue damage (also known as ADCC (antibody-dependent cell-mediated cytotoxicity)) • 2) Non-cytotoxic: antibodies can bind and interfere with normal function—for example: - Myasthenia gravis: anti-ACh (acetylcholine) receptor antibodies - Graves disease: anti-TSH receptor antibodies bind - Pernicious anemia: anti-IF (intrinsic factor) antibodies bind and thereby prevent IF from binding with vitamin B12 →

HBcAg

antigen associated with the *core* of Hep B.

HBsAg

antigen found on surface of HBV. Indicates. hep B infection Found in acute HBV chronic HBV (low and high)

SLE and complement

antigen-antibody complexes deposited in multiple tissues. Complement factors are activated and used up.

Caput medusae

appearance of distended and engorged paraumbilical veins, which are seen radiating from the umbilicus across the abdomen to join systemic veins.

pancreas and CF

approximately 85% to 90% of cases *Mild cases* Accumulations of eosinophilic mucus in the small ducts which plugs them, with some dilation of the exocrine glands. *Severe cases* Ducts are completely plugged, causing atrophy of the exocrine glands and progressive fibrosis Secondary diabetes from destruction of the islets occurs.

Diverticula

are outpouchings of the GI tract that communicate w/ the lumen—and are classed as true or false: A *true diverticulum* is composed of all 3 wall layers. In a *false diverticulum*, the pouch only involves the *mucosa and sometimes submucosa*. (not serosa) Most acquired diverticula are due to weakened muscularis externa → most are thus false

mucus lamina propria

areolar connective tissue containing many blood and lymphatic vessels, which are the routes by which nutrients absorbed into the GI tract reach the other tissues of the body. This layer supports the epithelium and binds it to the muscularis mucosae. The lamina propria also contains the majority of the cells of the mucosa- associated lymphatic tissue (MALT). MALT is present all along the GI tract, especially in the tonsils, small intestine, appendix, and large intestine

decreases O2 carrying capacity

arise w/ Hb loss or dysfunction. 1) anemia- decrease in RBC mass, Note: FiO2->PAO2--PaO2-> SaO2 are all normal. 2) CO poisoning- odorless, colorless gas w/ exposure to fire smoke, exhaust from cars, gas heaters.

benefits of breast feeding

balanced nutrition - passive immunity - increased bonding with mom - reduction in childhood IDDM

GCS

based on: eyes Vocalization motor function

Neutrophil adhesion

binding of leukocyte on vessel wall by cellular-adhesion molecules (ICAM, VCAM) upregulated on endothelium by TNF and IL-1 which bind integrins on leukocytes. (note, integrins upregulated by C5a and LTB4) This interaction results in firm adhesion Tight Binding: TNF and IL-1 released by macrophages and endothelial cells induce the endothelial expression of ligands for integrins, mainly VCAM-1 (the ligand for the VLA-4 integrin) and ICAM-1 (the ligand for the LFA-1 and Mac-1 integrins).

heparin

binds to antithrombin III to activate it, which then in turn acts to *inactivates thrombin* and Xa, as well as Factors 12, 11, 9, 7 (intrinsic pathway). Given for immediate anticoagulation (DVT/PE, MI, stroke): immediate onset if IV, ~30 minutes if SC Heparin does not cross the placenta, and thus is safer than warfarin in pregnancy.

other mycobacteriums besides TB

bovis microti

chorda tympani

branch of the facial nerve (cranial nerve VII) it both carries parasympathetic fibers to the submandibular ganglion as well as relays TASTE from the *anterior two thirds of the tongue.*

lingual nerve

branch of the mandibular nerve (cranial nerve V3). It relays general somatic afferent (GSA) sensory information from the *anterior two thirds of the tongue*

internal laryngeal nerve

branch of the vagus nerve (cranial nerve X). It relays general somatic afferent (general sensation) information from most of the posterior portion of the tongue as well as some special visceral afferent (taste) sensation from small area of the tongue just anterior to the epiglottis.

head injury amnesia

can be for events after the injury *anterograde amnesia* and for events immediately before the injury (*retrograde amnesia*. • anterograde amnesia is generally more severe and is related to the severity of the head injury. Memories during this period *do not recover*

AML subclassifications

can be subclassified by: 1) cytogenic abnormalities 2) lineage of myeloblasts 3) surface markers

Non-neoplastic polyps

can be: - hyperplastic - inflammatory - hamartomatous (e.g. Peutz-Jegher's) No risk of malignancy, but if seen on colonoscopy, they are taken out anyways during *colonoscopy* (b/c we can't tell for sure at that point).

Emphysema clinical features

can present with shortness of breath (earlier in life if PiZZ). Prolonged expiration with *pursed lips* . Problem is we have collapse of small airway... having *pursed lips* creases some backpressure to help keep wall open and let air *in and out*... so they are called *pink puffers* (slightly hypoxic)!!! - Weight loss (often b/c it is so much work to breathe) - Increased *AP diameter* of chest (*barrel chest*). (due to *collapsing in* tendency of lung, with *collapsing out* of chest wall)... normally this is *balanced* at the *functional residual capacity*.... but as you lose elastic recoil, and chest expands, the functional residual capacity increases. (!!!) Also note, if we get *fibrosis* of the lung, we *increase elastic recoil* which *decreases FRC*

oncogenes

cancer causing genes, when inappropriately activated, they turn a normal cell into a cancerous cell. Most derive from normal genes called protooncogenes.

Mesothelioma

cancer of the visceral or parietal pleural. Previous exposure to asbestos. Note, asbestos plus smoke does not multiple in risk of mesothelioma.... asbestos plus smoke multiplies risk of lung carcinoma.

what fungi is important in infection

candida albicans diploid yeast but cultures show hyphae (invade solid tissue and macro), pseudohyphae or budding yeast cells (this form disseminates easily

spinal satellite cells

capsule cells or support cells Are small, flattened glial (Schwann) cells, whose small dark nuclei are easily seen. Line the exterior surface of neurons in the peripheral n. system Derived from neuroectoderm (like the Schwann cells). They supply nutrients to the surrounding neurons and also have some structural function. Satellite cells also act as protective, cushioning cells.

interstitial nephritis

cause of *intra-renal azotemia* Drug induced *hypersensitivity* of interstitium....interstitial means the connective tissue between the tubules, and there is *inflammation* and inflammatory infiltrate here (edema + prominent mononuclear and eosinophilic infiltrate). Often due to NSAIDs, diuretics, penicillin.

central tolerance in thymus

central tolerance in the 1) thymus leads to T-cell (thymocyte) apoptosis or generation of regulatory T-cells. Stem cells enter the thymus and become *double positive* cells meaning they express both CD4 AND CD8... they ALSO express a TCR. They then progress to become *single positive* (CD4 OR CD8) and exit the thymus as *naive mature T-cells* *positive selection* means that the *double positive* cells are checked to see if they can bind MHC and Antigen. If they can recognize MHC, they progress to become *single positive cells*... if they cannot, they die via apoptosis. Next, for the cells that have survived, they are weeded out by NEGATIVE SELECTION. *negative selection* means that the *single T positive* cells are checked to see if they can bind *self antigen*. If they *avidly* bind it, they undergo apoptosis OR inactivated (by anergy). .... if they do not, they leave the thymus and proceed. Negative selection binds self antigens on either a *dendritic cell* or a *medullary epithelial cell* Summary: Survival of T-cells in thymus (1-5% of them) are ones that can recognize self-MHC proteins, but not self-peptides.

cervical nerve roots and level

cervical spinal nerves for each cervical spine travel ABOVE the vertebrae with the same number. For example C3 spinal nerve travels between CV2 and CV3. The only exception to this rule is C8 spinal nerve which actually travels between CV7 and TV1, and this is of course because there are only 7 cervical vertebrae. • Thoracic, lumbar, sacral, and coccygeal spinal nerves exit below their respective vertebrae. • Spinal nerves exit superiorly within the intervertebral foramen.

Chronic inflammation

characterized by lymphcytes and plasma cells in tissue, characterized by a walling-off of disease, with formation of granulomas (though not always!!) and fibrosis of the tissue. Most common stimuli is persistent infection(!) Also: -Infection w/virus', myobacteria, parasite, fungi -autoimmune disease - foreign material - some cancers

Bronchiectasis

chronic *dilation* of Bronchi and Bronchioles, where loss of tone results in air trapping (Obstructive), caused by destruction of muscle and elastic tissue Think that if I blew through a long straw, you'd feel air going out through other end... but if you blew through long pipe, you wouldn't feel air come out.

tropical sprue

chronic diarrheal disease (similar to celiac), possibly infectious, affects adults from the tropics, living close to equator. Patients present with diarrhea, steatorrhea, weight loss, and fat-soluble vitamin deficiencies. Treatment consists of antibiotics (tetracycline) (which it responds to, indicating *infection*!!!) and vitamin supplementation (including folate). Damage is *more in jejunum and ileum*, (!!!!) so you get Nutrient malabsorption, esp. folic acid, vitamin B12 and fat soluble Vitamins A, D, E and K

PTH osteoporosis

chronic exposure to high serum PTH concentrations (as seen with primary or secondary hyperparathyroidism) results in bone resorption. Given this observation, exogenous parathyroid hormone (PTH) would seem to be an unlikely candidate for the treatment of osteoporosis. However, intermittent administration of recombinant human PTH has been shown to stimulate bone formation more than resorption, at least over the first 12 months of treatment

medium arteries

considered more so to be *muscular arteries* are DISTRIBUTING vessels. These medium arteries contain *more tunica media smooth m.* than large elastic aa. Examples of muscular arteries include the radial artery and the splenic artery

neutrophil Phagocytosis

consumption of pathogens or necrotic tissue, enhanced by opsonins (IgG, C3b)... when neutropil sees IgG or C3b, it enhances this. pseudopods (like big arms extending out from leukocytes) extend out to form phagosomes which internalize the pathogen, and it merges with lysosome, forming phagolysosome.

Long bone

contains *compact bone* and *spongy (cancelous) bone*

tPA functions

converts plasminogen to plasmin which: 1) cleaves fibrin and serum fibrinogen 2) destroys coag factors 3) blocks platelet aggregation

HTN consequences

coronary artery disease, cerebrovascular accidents Hypertension, if untreated, leads to cardiac hypertrophy and, potentially, heart failure (hypertensive heart disease) Aortic dissection Renal failure. Retinopathy atherosclerosis

Examine head injury

cranial nerve exam labs, FBC, renal function CT, MRI,

ischemia

decreased blood flow through organ. Occurs via: 1- decreased arterial perfusion/blood flow (ie, atherosclerosis) 2) decreased venous drainage- blocking vein blocks flow of blood through bed which decreases amount of fresh blood, and thus amount of oxygen in organ (ie, Budd-Chiari syndrome-) 3) shock- generalized decrease in perfusion of vital organs- cardiogenic, hypovolemic, neurogenic, septic, anaphylactic

Metabolic acidosis

decreased pH, decreased bicarb, decreased PCO2 (compensation b/c of hyperventilation) LOSS of bicarb (diarrhea) or accumulation of acid (diabetes, exercise)

Rickets/Ostelmalacia

defective mineralization (calcium, phosphate), due to low levels vitamin D (acts on intestine, kidney, bone to resorb calcium and phosphate).

Osteomalacia

defective mineralization with low vitamin D in adults. Weak bones, increased fracture (ep weight bearing areas, hip, vertebrae). Decreaed 25 (OH) vitamin D (aka calcidiol) Decreased serum Ca (vit D deficiency), serum phosphate (vit D deficiency and PTH increase)) Increased PTH (b/c low calcium) and alkaline phosphatase. Alkaline phosphatase is always elevated whenever there is activation of osteoblasts. Alkaline phosphatase creates alkaline environment for osteoblasts.... here they are active, but ineffective b/c of poor mineralization.

Prinzmetal angina pectoris

described as *intermittent* chest pain *secondary to coronary artery vasospasms*. Unstable angina pectoris is also known as *variant angina pectoris*. Prinzmetal angina pectoris is *unrelated to physical activity* and episodes *usually occur at rest*, especially at night and early in the morning. Even though patients presenting with prinzmetal angina pectoris *may* have significant atherosclerosis, the coronary vasospasms causing the episodes are *not related* to atherosclerosis, thrombus formation, or physical activity. Is still REVERSIBLE injury.

. Frank-Starling relationship

describes the increases in stroke volume and cardiac output that occur in response to an increase in venous return or end-diastolic volume ■ is based on the length-tension relationship in the ventricle. Increases in end-diastolic volume cause an increase in ventricular fiber length, which produces an increase in developed tension. ■ is the mechanism that matches cardiac output to venous return. The greater the venous return, the greater the cardiac output. ■ Changes in contractility shift the Frank-Starling curve upward (increased contractility) or downward (decreased contractility). a. Increases in contractility cause an increase in cardiac output for any level of right atrial pressure or end-diastolic volume. b. Decreases in contractility cause a decrease in cardiac output for any level of right atrial pressure or end-diastolic volume.

cardiac thrombosis

develops on the *endocardium* (due to atherosclerosis or rheumatic heart) May occur in MI, A-fib, cardiomyopathy

Dementia

defined as an acquired deterioration in cognitive abilities that impair the successful performance of activities of daily living. Memory is the most common cognitive ability lost with dementia. other mental faculties are also affected in dementia; these include language, problem solving. Neuropsychiatric and social deficits also develop in many dementia syndromes, resulting in depression, withdrawal, hallucinations, delusions. The most common forms of dementia are progressive. Causes: • Alzheimer's disease • Vascular dementia • Multi-infarct - alcoholism

interstitial (atypical) pneumonia

diffuse patchy infiltrates, localized to interstitial areas.... *no major consolidation*. Presents with *atypical* signs- mild symptoms, minimal sputum, cough, low fever.

spongy (cancellous) bone

does NOT contain osteons consists of lamellae arranged in an irregular lattice called trabeculae Trabeculae have lacunae which contain osteocytes and canaliculi and receive nourishment directly from blood in medullary cavities. They make up most of flat bones. Oriented *along the lines of stress*

causes of osteoporosis

drugs (ie, corticosteroids) Hypogonadism (from AN, hypopituitarism)

Ischemia acute tubular necrosis

due to *decreased blood supply* which results in necrosis of the tubules. Remember the tubules have very high energy requirements, especially the *proximal tubule* and the *medullary segment of thick ascending limb* It is often *preceded* by *prerenal azotemia*.

What causes bronchiectasis ?

due to *necrotizing* infection/inflammation of bronchi (large airway) ie: - cystic fibrosis (thick mucus secretions cause mucus plugging, and when you block a tube you get infection!!!) -Kartagener's syndrome - tumor/foreign body -Allergic bronchopulmonary *aspergillosis* (hypertensitivity in larger airways to *aspergillosis* classically seen in 1) asthmatics and 2) CF patients. *aspergillosis* comes in, get reaction and damage airway. - Infectious causes include TB (most common) as well as S. aureus and H. flu.

most common cause of anaphylaxis

food allergy (ie, peanuts, eggs, shellfish) venom from bee sting latex

Hypercoagulable state in nephrotic syndrome

due to preferential loss of anticoagulants like antithrombin III, protein C and protein S in urine → ↑ risk of thrombosis (eg, renal vein thrombosis, especially in membranous nephropathy) and ↑ risk of thromboembolic complications also vascular stasis, an increase in hepatic production of fibrinogen and other clotting factors, increased plasma platelet production (as an acute phase reactant), and increased platelet aggregation. The coagulopathy manifests with thromboembolic events.

Metabolic acidosis causes

due to: 1) increased acid generation (ie, exercise, ketoacidosis) 2) loss of bicarb 3) diminished renal acid secretion

hematologic malignancies

either lymphoid disorders, or myeloid disorders Lymphoid disorders are either -acute (ALL) - chronic [(a) CLL (b) multiple myeloma (c) non/Hodgkins] myeloid disorders are either: - acute (AML) - Chronic [either myeloproliferative (CML), or myelodysplasia]

'healthy' carrier

elevated HbsAg and Anti HBcore antibody igG (Anti HBc IgG)

Ectopic pregnancy

embryo implants outside the uterine cavity. The most common site is the ampullary portion of the fallopian tube (80%). Nontubal sites of pregnancy are a rare occurrence: abdominal pregnancies, ovarian, and cervical sites associated with PID with chronic salpingitis - adhesions from appendicitis - previous IUD use

COPD classically includes

emphysema chronic bronchitis

Lymphadenopathy (LAD) !!!

enlarged lymph nodes. - Painful LAD usually with acute infection - Painless LAD with: - chronic inflammation (autoimmune disease) metastatic carcinoma, or lymphoma Lymph node has 3 regions: 1) cortex - WBC's are packed in the follicles and live here!! Follicle is surrounded by MANTLE, and sometimes MARGIN. This region hyperplases in RA, and EARLY (!) HIV (because follicular dendritic cells are also CD4+) 2) cortex (T-cells live here, so VIRAL infection, ie EBV, causes hyperplasia here) 3) medulla (sinus histiocytes live here, they enlarge when a lymph node is DRAINING a REGION of cancer)

CK-MB

enzyme that reversibly transfers a phosphate group from creatine phosphate to ADP. Mostly found in cardiac muscle but can also be found in skeletal muscle ∴ not as specific as troponins in diagnosing acute MI Begins to rise 4-6 hours after onset. - peaks at 24 hours - and returns to normal within 2-3 days Re-elevation of CK-MB can diagnose a *re-infarction between *3 and 10 days post myocardial infarction, however *troponin cannot diagnose re-infarction* between days 3 and 10 because troponin is still elevated from the first infarction!

complications of GERD

esophageal stricture: any process that causes esophageal inflammation/fibrosis 70-80% from GERD → esophagitis /ulceration→ stricture (narrowing of lumen) Note: with an ulcer it knocks out both mucosa, and chunk of submucosa (so stem cells are knocked out too), so the ulcer heals by *fibrosis* Feared complication is *Barrett's esophagus*

Edema

excess fluid outflow into interstitium commonly caused by: • ↑ capillary pressure (↑ Pc; heart failure) • ↓ plasma proteins (↓ 1πc; nephrotic syndrome, liver failure) • ↑capillary permeability (↑Kf; toxins, infections, burns) • ↑ interstitial fluid colloid osmotic pressure (↑πi; lymphatic blockage)

Conjugate vaccines

for bacterium that possesses an outer coating of sugar molecules called polysaccharides. Polysaccharide coatings disguise a bacterium's antigens so that the immature immune systems of infants and younger children can't recognize or respond to them. Conjugate vaccines, a special type of subunit vaccine, get around this problem.

complications of sickling

extravascular hemolysis leads to anemia, Jaundice, high UCB Intravascular hemolysis (minimal, but some) decreases haptoglobin, target cells are formed which appear on blood smear. Both extra and intravascular hemolysis causes massive erythroid hyperplasia and expansion of hematopoiesis. -expansion of hematopoiesis into skull and facial bones ("crew cut" or "chipmunk" head/face). -extramedullary hematopoiesis with hepatomegaly (since spleen gets knocked out, liver starts hematopoiesis). -irreversible sickling of RBC's - Risk of Viral infection (esp. parvovirus B19) → aplastic crises with major ↓ in hemoglobin concentration

Esophageal varicies

extremely dilated sub-mucosal veins in the lower 1/3 of the esophagus. Note: most of esophagus drains by *azyous vein* into SVC* , but SOME drains *left gastric vein into portal vein*. *Portal hypertension* (commonly due to cirrhosis) causes backup of blood in portal hypertension, left gastric vein, and thus dilated sub-mucosal veins. Likely to result in *hemoptysis* and *hematemesis* (vomiting flood)

late phase eosinophil rxn cytokines

favored by IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5 is the most potent eosinophil- activating cytokine known.

Hep A spread and complications

fecal-oral, uncooked food/seafood, contaminated water. Commonly TRAVELERS. Often subclinical- Most likely hepatitis to produce Jaundice -most recover, liver damage reversed, no carrier state

Arterio*lo*sclerosis

form of arteriosclerosis affecting the *small arteries and arterioles*, associated with HTN (hypertension) and diabetes mellitus.

Kidney JGA

formed by - The terminal portion of the afferent arteriole, - The first portion of the efferent arteriole, - The extraglomerular mesangium (between both arterioles) and The JGA is innervated by the sympathetic system. Under the control of blood pressure, autonomic nerves, hormones, salt balance, and local stimuli, particularly the composition of tubular fluid at the *macula densa.* Juxtaglomerular cells (J cells) secrete renin

Pott fracture

fracture of distal fibula

CCK

from the *L-cells* in the duodenum and jejunum. Stimuli for release is mostly FA's in intestinal lumen, but also small peptide/aa's and monoglycerides in lumen. It stimulates: 1) It stimulates the acinar cells of the pancreas to release digestive enzymes and stimulates the secretion of a juice rich in pancreatic digestive enzymes Slows gastric emptying (high CCK decreases hunger)

G cells secrete

gastrin, this mostly occurs in the *antrum* of stomach. Gastrin acts to: 1) increase HCl secretion from the *parietal cell*. 2) stimulate growth of gastric mucosa to make a clear, soluble mucus with high concentration of bicarb. Stimulated by: 1) *vagus nerve* release of *GRP- gastrin releasing peptide* 2) Protein in stomach 3) gastric distension

proto-oncogenes

genes that are essential for cell growth and differentiation. mutations of them form ONCOGENES. Oncogenes lead to unregulated cell growth. Oncogenes are cancer producing genes derived from normal components of the human genome (i.e., proto-oncogenes) which are normally suppressed. These genes gain function leading to cancer (need damage to only 1 allele)

causes of a seizure

genetic error of metabolism meningitis MS alcohol withdrawl

Secondary hemostasis

goal is to stabilize the WEAK platelet plug. End product of coagulation cascade is thrombin. Thrombin converts fibrinogen into fibrin, which is then cross linked, stabilizes the platelet plug. Many coagulation factors are secreted as zymogens. Upon activation, they become serine proteases that can activate downstream factors Many reactions in the cascade require Ca2+ and platelet phospholipid as cofactors

cumulus oophurus

granulosa cells form a protrusion towards the interior of the antrum - Cumulus oophurus - containing the oocyte .

heart changes with age

hardening of arteries, and heart enlargement valvular calcification

Hep B structure

hepadnavirus- family of enveloped, double-stranded viruses which can cause liver infections in humans and animals —enveloped (HbsAg) - Icosahedral capsid (core protein (HBcAg) - circular, partially dsDNA. DNA polymerase has both RNA-dependent (reverse transcriptase, even though it is NOT a retrovirus) and DNA-dependent activity. smallest DNA virus known but capable of encoding surface (envelope) protein (HBsAg),

Mitral regurgitation murmur

high pitched holo/*pan systolic* murmur at the *apex*, and *radiating to the axilla*.!!!!!!! Mitral regurgitation, also known as mitral insufficiency, refers to the backflow of LV→LA during *systole*. Louder with squatting (squatting increases afterload so more regurge) and expiration (more blood into LA then LV) Mitral valve prolapse is the *most common* cause of mitral regurgitation. can also be caused by *papillary muscle damage* post myocardial infarction (MI). Infectious causes of mitral regurgitation include *rheumatic heart disease* and infective endocarditis with valvular damage. the murmur of mitral regurgitation may co-occur with a mid-systolic click. Mitral regurgitation is associated with an S3 heart sound.

CLL complications

hypogammaglobulinemia (cells do not produce immunoglobulin- so infection is most common cause of death) - autoimmune hemolytic anemia (warm IgG mediated) Infiltration of marrow, spleen & liver → hepatosplenomegaly

Hep A structure

icornaviridae family. is an unenveloped (naked capsid), single-stranded RNA virus with a cubic (icosahedral) symmetry.

X linked recessive

ie red/green color blindness, DMD 1. Males affected - females are carriers, Males only have one X-Chromosome - so if a male inherits a diseased X-Chromosome, he doesn't have another good X-Chromosome to hide the effects of that mutation. In females - her other good X-Chromosome will hide effects of mutation. 2. Rarely females affected - must inherit TWO mutant X-Chromosomes. 3. Skips generation 4. Unaffected parents - usually mother is an asymptomatic carrier 5. No male to male transmission as the Y chromosome is inherited from the father. 6. OBLIGATE CARRIERS: Mothers of affected sons, and daughters of affected fathers!!

X linked dominant inheritance

ie, Fragile X 1. Affects both sexes, phenotype more mild/variable in females 2. Child of affected female 50% chance of being affected but affected male has all affected daughters, no affected sons. 3. No male —> male transmission (Y chromosome inherited) 4. Appears in every generation --> DOMINANT

band neutrophil aka stab cell

immature neutrophil They have a band/rod shape nuclei instead of a segmented nuclei typical of a mature cell.

Respiratory alkalosis

increased pH, decreased pCO2, decreased bicarb (renal decrease, compensation) Hyperventilation due to oxygen deficiency, anxiety

metabolic alkalosis

increased pH, increased bicarb, increased PCO2 (compensation, slow breathing) LOSS of acid (vomiting)

male puberty changes

increased testicullar size, penis length

2 complications of BPH

infection and cystitis hydronephrosis

leukocytosis seen in

infections leukemia tramua stress tissue necrosis/inflammation

Inflammatory back pain

infective lesions of spine Ankylosing spondylitis (chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures.... can eventually fuse spine)

Hyper-osmotic overhydration

ingest excess NaCl. ECF volume increases, and ECF osmolarity increases. Thus, there is a fluid shift of ICF --> ECF. ICF fluid volume decreases ICF fluit osmolarity increases

paracetamol mechanism and toxicity

inhibits PG synthesis in CNS Does not really act on COX in peripheral tissue • Following a therapeutic dose, it is mostly converted to nontoxic metabolites via Phase II metabolism by conjugation with sulfate and glucuronide, with a small portion being oxidized via the cytochrome P450 enzyme system. • Cytochromes P450 converts approximately 5% of paracetamol to a highly-reactive intermediary metabolite (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione. Excess NAPQI or decreased glutathione (ie, chronic alcoholism) allows NAPQI to bind to cellular proteins and lipid bilayer of the hepatocyte membrane, causing an oxidative cascade and inflammatory damage.

cancer spread

initial tumor over basement membrane is *carcinoma in situ* cancer cell becomes capable of invasion by expression of *adhesion mollecules*, namedly *integrin* to bind to ECM. The tumor then binds. Once bound, it releases proteolytic enzymes called MMPs to degrade the ECM. Then it can metastasize by blood or lymph. note: cancer cells LACK *E-cadherin*, which allows them to detach from each other, and become invasive.

Healing

initiated when inflammation begins... occurs via combination of REGENERATION and REPAIR. Regeneration- replacement of damaged tissue with native tissue, but depends on regenerative capacity of tissue. 3 types of tissues based on regenerative capacity: 1) Labile 2) Stable (quiescent) 3) Permanent

Hodgkin's lymphoma

instead of having a whole mass of malignant cells, instead, you have RARE neoplastic cells called Reed-Sternberg cells (!!!) which secrete cytokines which draw in other inflammatory cells which results in production of a mass. Prognosis negatively correlates with number of RS cells, but positively correlates with number of reactive lymphocytes More RS cells → worse prognosis More lymphocytes → better prognosis

Intussusception

invagination of one portion of the bowel into itself—proximal portion usually dragged into distal portion by peristalsis. As you drag it in, you also drag in blood supply, so this lads to infarction, *currant jelly stools* Assoc w/a "lead point" - an intraluminal mass that peristalsis can "hook onto" and drag bowel during peristalsis.

investigate seizures

investigation of seizures. Bloods Routine blood studies are indicated to identify the more common metabolic causes of seizures, such as abnormalities in: • Electrolytes, • Glucose, • Calcium, • Magnesium, • and hepatic or renal disease. EEG Imaging: MRI >> CT

cholesteatoma

is a benign growth in an abnormal location such as the middle ear or petrous apex a chronic infection or direct trauma are the leading causes .

Goiter

is an enlarged thyroid gland, caused by excessive stimulation of TSH receptors, resulting in hyperplasia. It can be seen in different disease states, such as Graves' disease and iodine deficiency. Iodine deficiency is fairly uncommon in the US.

Lambert-Eaton syndrome

is caused by autoantibodies against voltage-gated calcium channels, which inhibit release of acetylcholine at the neuromuscular junction.

Atrial natriuretic peptide (ANP)

is released from the atria in response to an increase in blood volume and atrial pressure. ■ causes relaxation of vascular smooth muscle, dilation of the arterioles, and decreased TPR. ■ causes increased excretion of Na+ and water by the kidney, which reduces blood volume and attempts to bring arterial pressure down to normal. ■ inhibits renin secretion.

Myocardial infarction

leads to *necrosis* (irreversible) of cardiac myocytes, classically due to *rupture of an atherosclerotic plaque* with thrombosis and *complete* occlusion of coronary artery. Other causes include coronary artery vasospasm, emboli,

PR interval

is the interval from the beginning of the P wave to the beginning of the Q wave (initial depolarization of the ventricle). ■ varies with conduction velocity through the atrioventricular (AV) node. For example, if AVnodal conduction decreases (as in heart block), the PR interval increases. ■ is decreased (i.e., increased conduction velocity through AV node) by stimulation of the sympathetic nervous system. ■ is increased (i.e., decreased conduction velocity through AV node) by stimulation of the parasympathetic nervous system.

FVC

is the maximum amount of air a person can expel from the lungs after a maximum inhalation. (think blowing out candles of a birthday cake) It is equal to the sum of: inspiratory reserve volume + tidal volume + expiratory reserve volume.

Asthma and spirometry

it is obstructive so ↓ FEV1/FVC ratio (Normal 80%... so in obstructive it is <80%) BUT Asthmatics should respond with an *increase of FEV1 greater than 12%* after bronchodilator administration

hyaline arteriolosclerosis in kidney

leads to glomerulosclerosis Preferential involvement of efferent arteriole increases pressure in glomerulus leading to glomerular hyperfiltration injury with microalbuminuria, leading to sclerosis of mesangium in the glomerulus, that eventually progresses to nephrotic syndrome, characterized by KIimmelstiel-Wilson nodules. Also, some arteriolosclerosis of afferent arteriole, decreasing blood supply to glomerulus and leading to diffuse sclerosis of it.

heart valve flaps (leaflets vs cusps)

leaflets (in the tricuspid and mitral valves) or cusps (in the aortic and pulmonary valves, also known as the semilunar valves).

O2 independent killing

less effective, occurs via enzymes present in leukocyte. Occurs via enzymes present in leukocyte secondary granules (ie, lysozyme).

Neutrophil transmigration and chemotaxis

leukocytes transmigrrate across endothelium of postcapillary venules, PECAM plays the major role in diapedesis.

common causes of splenomegaly

liver disease (cirrhosis, hepatitis) -infections (mono, AIDS) - blood cell disorders (sickle cell) - cancers

Budd-Chiari syndrome

liver infarct/thrombosis secondary to hepatic vein obstruction - Blood flows in through portal vein, obstructed in leaving Painful hepatomegaly, ascites, necrosis of liver Caused by HCC

hypoxemia-

low partial pressure of O2 in blood (PaO2 < 60mm Hg, SaO2 <90%), is cause of hypoxia Buildup of CO2 in lung (hypoventilation, COPD, interstitial fibrosis of lung, ) all decrease PAO2 (big A) which decreases PaO2. Also V/Q mismatch- blood bypasses oxygenated lung (ie, shunt) or oxygenated air cannot reach blood (ventilation problem like atelectasis)

compact bone

made up of Haversian systems (osteons) which run parallel to long axis of bone Haversian canal contains vessels. It is surrounded by the circles of lamellae (calcified ECM). Canaliculi are small channels which radiate from the lacunae and contain projections to the osteocytes, creating a network to transfer nutrients/waste to/from the osteocytes.

SLE signs

malar "butterfly" rash sparing the nasolabial folds - joint pain (link with RA) - Ulcerations and bullae formation • Haemolytic anaemia • Thrombocytopenia

Paget's disease

massive bone turnover due to ↑ osteoclastic and ↑ osteoblastic activity → abnormal bone architecture Usually seen in late adulthood (~60) Localized process (does NOT involve whole skeleton) Bone pain, increasing hat size (commonly affects skull), lion-like faces (facial bones thicken) Isolated, elevated, alkaline phosphatase (everything else normal) High output cardiac failure due to formation of AV shunts, heart has to push through. Osteosarcoma- 'blasts' can mutate and form osteosarcoma, malignant tumor of osteoblasts

repair and regeneration

mediated by paracrine signalling via growth factors. Interaction of factors with receptors results in gene expression and cellular growth. Ie, TGF-α- epithelial and fibroblast growth factor TGF-β- important fibroblast growth factor, inhibits inflammation PDGF- endothelium, smooth muscle, fibroblast growth factor FGF- angiogenesis, skeletal development VEGF- angiogenesis

Thalassemias

microcytic anemias that are due to defects in synthesis (!!!!) of α- or β-globin chains of hemoglobin. Decreased globin leads to decreased hemoglobin Note: it is decreases synthesis of the chains which is a thalassemia... alterations of the globin chain (ie, sickle cell) are not considered a thalassemia. Clinically significant thalassemias are inherited in an autosomal recessive fashion. Thalassemia carriers are protected against Plasmodium falciparum (!!) malaria !!! divided into α-Thalassemia or β-Thalassemia

Accumulation of mature myeloid cells

myeloproliferative disorder: 1. RBC overproduction: polycythemia vera 2. Granulocyte overproduction: CML 3. Megakaryocytes overproduced: essential thrombocythemia 4. Monocyte overproduction:

zone 2 liver

necrosis in yellow fever.

fourth degree burns

o Fourth (full thickness) Depth: injury to underlying tissue structures (eg. muscle, bone) CF: insensate (nerve endings destroyed), hard leathery eschar thati s black, grey. White or cherry, no hair, may see thrombosed veins

second degree burns

o Second (superficial-partial thickness) - Depth: into superficial dermis PINK - CF: pain, sens intact, erythema, blisters, sluggish cap refill, hair follicles present o Second (deep-partial thickness) -nDepth: into deep reticular dermis BOTCHY RED - CF: insensate, does not blanch (no cap refill), some hair follicles, softer than full thickness

third degree burns

o Third (full thickness) Depth: through dermis WHITE CF: insensate (nerve endings destroyed), hard leathery eschar thati s black, grey. White or cherry, no hair, may see thrombosed veins

Hemianopia with macular sparing

occlusion of the posterior cerebral artery produces contralateral hemianopia with macular sparing (macular area of the cortex is supplied by both posterior cerebral artery and middle cerebral artery so an occlusion of the PCA will spare the macula due to collateral blood supply from the MCA)

Urinary tract infections

occur anywhere in urethra, bladder, or kidneys. Usually due to *ascending infection* in urethra that works its way up. Higher incidence in women due to shorter length of female urethra Higher incidence during pregnancy, sex, catheter Most frequently involves normal flora of colon, such as E. coli Lower UTI: cystitis (inflammation of bladder), prostatitis, urethritis Upper UTI: pyelonephritis (pyelo = "pelvis"), so it is infection of *kidney*

superficial venous thrombosis

occur in varicosities, rarely embolize, may cause local congestion, swelling, pain, tenderness.... predispose to infection and ulcers

inhibition of clotting cascade

occurs via activated Protein C, and Antithrombin III. tPA (tissue plasminogen activator) disrupts existing clots. Because Protein C has the shortest half life, its levels are quickly diminished when warfarin therapy is initiated. This leads to a transient hypercoagulable state characterized by skin necrosis. Heparin or Enoxaparin therapy must be initiated simultaneously. This is known as the "heparin bridge" and is always done when initiating warfarin therapy.

Pneumothorax

occurs when air enters the *pleural cavity* causing the *lung to collapse*. There are 2 ways this generally occurs: Air can enter the pleural space through the chest wall as a result of trauma. Air enters pleural space from the lung parenchyma through the visceral pleura. Can be: - Primary spontaneous - Secondary spontaneous - tension

Cleft lip

occurs when the *maxillary prominence* fails to fuse with the *medial nasal prominence*. The underlying somitomeric mesoderm and neural crest fail to expand, resulting in a persistent labial groove. Cleft lip can be bilateral or unilateral. Unilateral cleft lip is the most common congenital malformation of the head and neck.

Ischemic Bowel Disease

occurs when the flow of any of the major blood vessels feeding the small and large intestine—celiac, SMA, IMA—is severely compromised. This leads to ischemia, hemorrhage, necrosis and infarction of bowel. There are 3 degrees of infarction: - Mucosal infarction - Mural (submucosal infarction) - Transmural infarction

Cleft palate

occurs when there is failure of fusion of the lateral palatine shelves, the nasal septum, and/or median palatine processes Clefts anterior to the incisive foramen are anterior cleft palate defects. Clefts posterior to the incisive foramen are posterior cleft palate defects. An anterior cleft palate occurs when the palatine shelves fail to fuse with the primary palate. A posterior cleft palate occurs when the palatine shelves fail to fuse with each other and with the nasal septum. An anteroposterior cleft palate is a combination of both anterior and posterior palatal defects -prone to hearing loss.

impacted fracture

one end of fractured bone is forcefully driven into other

risk factors for esophageal squamous carcinoma

one word: *irritation* - alcohol and tobacco - VERY hot tea (high cancer in south China and Iran where they drink hot tea) - Achalasia (rotting food stuck in esophagus irritates mucosa) - Esophageal webs (rotting food)

Window phase

only Anti- HBV core antibody IgM (anti-HBc IgM)

Early HB phase

only Hep B surface antigen (HBsAg) raised

Mitral stenosis murmur

opening snap followed by an early mid-diastolic, low pitched rumbling. Best heart at mitral area. The time between the second heart sound and the opening snap decreases as the stenosis becomes more severe. Patients may have a loud first heart sound.

Hep B transmission

oral-fecal (possible but not common) - sexual ( Approximately 50% of infections in the United States are sexually transmitted) - Primarily spread via blood (IV- Drug abuse 40%-60% of cases overall)

hypoglossus

originates from the hyoid bone and inserts into the side of the tongue. *It acts to depress the tongue during swallowing.

genioglossus

originates from the mandible and inserts into the entire dorsum of the tongue. When *acting alone*, it acts to *deviate the tongue to the contralateral side*.

Palatoglossus

originates from the soft palate and inserts into the side of the tongue. It acts to *elevate the tongue* and is innervated by the vagus nerve (cranial nerve X). It is the only extrinsic muscle of the tongue not innervated by the hypoglossal nerve (cranial nerve XII).

disease risk with menopause

osteoporosis CVD Depression

screen for bowel cancer

over 50:: FOBT every year flexible sigmoisoscopy every 5 years Colonoscopy

Bcl2 overexpression and lymphoma

overexpressed in follicular lymphoma. (B-cell lymphoma, second most common non-Hodgkin lymphoma) Classically presents in adults with "waxing and waning" lymphadenopathy "Follicular" — Fourteen: t(14;18) translocation → juxtaposition of bcl-2 (an oncogene that inhibits apoptosis) next to the IgH locus. This leads to overexpression of BCL2 → ↓ apoptosis, thus leading to a lymphoma. Lymph nodes are obliterated by characteristic neoplastic nodules: uniform, round, and isolated. These nodules are comprised of B-cells recapitulating the germinal centers of lymphoid follicles

pathogenesis of ischemic bowel disease

pathogenesis of the damage occurs in two phases: 1) Initial hypoxic injury followed by 2) reperfusion injury. The onset of hypoperfusion or obstruction causes the initial hypoxic injury. However, the epithelial cells lining the mucosa in the intestine are relatively resistant to transient hypoxia. When blood flow is restored, reperfusion injury occurs, and this is what causes the greatest extent of damage. Recall that reperfusion injury produces free radical production, release of inflammatory cytokines and oxidative stress.

treat hep B and C

pegylated interferon- interfere with virus ability to infect cells. Made via recombinant DNA technology, the "pegylated" increases size of the molecule, lengthening drug action. Entecavir- guanosine analogue approved to treat HBV... phosphyrlated to triphosphate, comptes for viral reverse transcriptase Lamivudine- cytosine analogue, inhibitor of both HBV DNA polymerase and HIV reserve transcriptase

Ghrelin

peptide hormone secreted primarily by the P/D1 cells in the fundus of the stomach and has effects antagonistic to those of leptin. Specific effects of ghrelin include: 1) ↑ GH (growth hormone), cortisol, ACTH and prolactin secretion 2) Food seeking via the vagus nerve of the PNS and the arcuate nucleus of the hypothalamus in the CNS. Ghrelin levels drop shortly after a meal, and increase before a meal and during fasting. Gastric bypass surgery → decrease in ghrelin levels. Clinical Correlate: In Prader-Willi patients, ghrelin levels do not decrease after a meal → continuous food-seeking, weight gain.

other causes of Vitamin B12 deficiency

pernicious anemia - Pancreatic insufficiency- pancreas produces the enzymes to hydrolyze the R-factor bond and B12 in small bowel. B12 then binds IF. - Damage to terminal ileum (B12 absorbed here) as seen in Crohn's, or the fish tapeworm Diphyllobothrium latum. - Dietary deficiency is rare except in vegans!!

clinical features of chronic bronchitis

productive cough (obviously). ↑ PaCO2 and ↓PaO2 which presents as *cyanosis* - Increased risk in infection. Note, principle of pathology is anytime you block a tube, you have high risk of infection behind it. (ie, here, BPH and urinary infection, wax ear and infection). Also increased risk of *cor pulmonale* as a result of *hypoxia*, which causes *vasoconstriction of pulmonary arterioles* → ↑ afterload., and ↑ Afterload can eventually cause *RV failure*.

Decay accelerating factor

protein on human cells, (DAF, also known as CD55) inhibits the assembly of C3 convertases. Prevents inappropriate activation of complement. Deficiency of DAF leads to complement-mediated lysis of RBCs → paroxysmal nocturnal hemoglobinuria (PNH)

Cardiac enzyme troponin

protein that helps control interaction between actin and myosin in skeletal and cardiac muscle. Relative to other biomarkers (eg, CK-MB, LDH), cardiac forms of *troponin I* (cTnI) and *troponin T* (cTnT) have *↑ sensitivity for myocardial damage*, and are ∴ currently the *preferred biomarkers* for detecting myocardial necrosis Begins to *rise 2-4 hours after onset* - peaks between ~24 hours - remains elevated for 7-10 days - returns to normal within 10-14 days

glossopharyngeal nerve

provides *general sensation and taste sensation* to the *posterior 1/3* of the tongue.

Acute Hep B infection

raised -Hep B surface antigen (HbSAg) - Hep B e-antigen (HBeAG) and HBV DNA which are the infective particles - Anti Hep B core antibody IgM

Keloid

raised scar caused by excessive type III collagen synthesis during tissue repair; common in blacks. This collagen deposition, seen as the acellular fibrous area beneath the dermis, leads to a raised lesion as it is displaced up by fibrous nodule. Keloids extend beyond the borders of the original wound (vs. hypertrophic scars, which remain limited to the area of the wound) Although there is excessive synthesis of type III collagen early in keloid formation, this type III collagen is slowly converted to type I. Thus, type III collagen predominates early in keloid formation. Examples of causes of keloids: - following skin trauma (classic example: earlobe piercing) - complication of tertiary stage Treponema pertenue (yaws) infection

risk factors for CR

red meats, saturated fats, smoking, alcohol low fibre, fruit/vegetables.

striations

reflect the arrangement of protein myofilaments in a muscle cell.

eye changes with age

refraction error increases rididity of lens cataracts formation decreased number of rods and cones

TB symptoms

related to cytokines released by activated macrophages. persistent cough Fever Night sweats haemoptysis weight loss

*Type B- chronic atropic H-pylori*

represents *most common gastritis* (90% of cases*. H. pylori colonizes (but does not invade!!) mucus layer lining. H-pylori *produces ureases and proteases* which causes inflammation and weakens mucosal defenses. Happens most often in *antrum*. Presents w/ epigastric pain, risk for ulceration and BOTH risk for *gastric adenocarcinoma* (intestinal metaplasia from chronic inflammation) AND *MALT lymphoma*, a *primary B cell lymphoma* of the stomach.

Resolution

resolve exudate, lung heals by *type 2 pneumonocyte* which has stem cells, and fibrin is laid down.

Mitral stenosis complications

results in increased left atrium pressures and thus *left atria dilation* (volume overload because all blood in LA cannot be pushed into LV) and thus pulmonary congestion and pulmonary hypertension.The increase in left-atrial pressure eventually causes pulmonary vascular congestion, which causes exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea, which are the most common presenting symptoms. Remember, Pulmonary congestion causes- 1) edema etc.... 2) alveolar hemmorage (capillaries rupture, macrophages consume them giving *heart failure cells* (hemosiderin laden macrophages)... hemoptysis can occur. dilation of LA gives *Atrial fibrillation*, thrombus or thromboembolism may occur.

right (ascending) vs left (descending) side colon tumors

right (ascending) is more likely to be a polypoid exophytic mass, iron deficiency anemia, weakness. Bleeds *into* the stool, which may not alter its appearance. Left (descending) is more likely to show annular, encircling lesions 'apple core' lesion on barium, and 'napkin ring' gross lesion. More likely to cause *obstruction* because it has a smaller diameter, collicky pain, Feces is harder, bright red blood streak stool.

Cardiac enzymes

roponin I, Troponin T - CK- MB -myoglobin - AST

Myelin basic protein

s also often present in the CSF during periods of active disease in MS.... and indicates the presence of active myelin breakdown.

Mantoux test

screening tool for tuberculosis (TB). It is one of the major tuberculin skin tests used around the world, Tuberculin PPD (purified protein derivative) is injected into the dermis. A small bleb develops, but is absorbed within a short time. (b) After 48 to 72 hours, the skin reaction is read based on the size of the raised area. A reaction of less than 5 mm is negative in all patients.

Glaucoma

second leading cause of blindness): increase in intraocular pressure (IOP) due to the disruption in the balance of aqueous humor production by the ciliary processes and drainage by the trabecular meshwork → leads to *optic nerve damage* Leads to *tunnel vision*, which is NOT the same as bitemporal hemianopia.

Hemoglobin's oxygen dissociation curve

sigmoidal: the tetramer flips between 2 conformations Deoxy or T (Taut) form: low O2 affinity Oxy or R (Relaxed) form: high (↑ 300x) O2 affinity When 2 O2 molecules are bound to the T form, conformation switches to R and all 4 sites can be filled The T to R shift occurs under conditions of high oxygen tension (i.e. the lungs) and the R to T shift occurs under conditions of low oxygen tension. Lung: High O2 → oxygenated Hb. Tissues: Low O2 → deoxygenated Hb (Bohr effect: ↑ CO2 and/or H+ concentration stabilizes deoxygenated conformation).

urticaria (aka hives)

skin rash notable for pale red, raised, itchy bumps. characterised by localised mast cell degranulation and resultant dermal microvascular hyperpermeability. • This gives rise to pruritic oedematous plaques called wheals.

Berry aneurysm

small *saccular* lesions in the *circle of Willis* that develop at sites of *congenital medial weakness*.... rupture causes *subarachnoid hemorrhage, and is unrelated to atherosclerosis* Defect at the *junction of communicating branches* with main cerebral vessels because *these areas lack internal elastic lamina and smooth muscle (tunica media) layers*.

cauda equina

spinal cord terminates in the conus medullaris at level of L1 vertebrae, and the remaining nerve roots L2, L3, L4, L5, S1-5) descend in the vertebral canal. CE syndrome- results in neurological signs not confined to one nerve root, such as loss of sphincter control and perineal sensation, and/or difficulty walking. sexual dysfunction, bladder dysfunction, saddle anasthesia. caused by: congenital lumbar stenosis

name bacteria in food poisoning

staph aureus clostridium perfringes salmonella yersinia entercollitica bacillus cereus E coli Campylobacter jejuni:

Disruption in blood flow

stasis/turbulence. ie, immobilization - cardiac wall dysfunction (arrythmia or a-fib) - aneurysm (flow is slightly irregular in aneurysm)

Spondylolysis

stress fracture of pars interarticularis (area between peddicle and lamina). Most commonly L4 or L5 vertebrae.

Hyperextension of the neck (whiplash)

stretches the anterior longitudinal ligament and injures the cervical vertebrae (most commonly C4-C5 or C5-C6)

functions of bone

support mineral homeostasis Blood buffering movement blood cell production TAG storage

diabetes diagnosis

symptoms, plus random plasma glucose > 11, or fasting > 7.

fibrinolytic system

system dissolves small, inappropriate clots; it also dissolves clots at a site of damage once the damage is repaired. Dissolution of a clot is called fibrinolysis. When a clot is formed, an inactive plasma enzyme called *plasminogen is incorporated into the clot*. Both body tissues and blood contain substances that can activate plasminogen to plasmin or fibrinolysin, an active plasma enzyme. Among these substances are thrombin, activated factor XII, and tissue plasminogen activator (t-PA), which is synthesized in endothelial cells of most tissues and liberated into the blood. Once plasmin is formed, it can dissolve the clot by digesting fibrin threads and inactivating substances.

Primary amyloidosis

systemic deposition of AL amyloid (deriged from Ig light chain). Associated with plasma cell dyscrasias (abnormalities of plasma cell) where the light chain can be overproduced, leaks out into blood, can become disfolded and deposit. Also with multiple myeloma and Waldenstrom's macroglobulinemia.

fibrinolysis

tPA activates plasminogen which is cleaved to plasmin, which is a potent fibrinolytic agent and lyses clots that are already formed. Plasmin: 1) Cleaves fibrin and serum fibrinogen 2) destroys coagulation factors 3) Blocks platelet aggregation Plasmin is inactivated by alpha-2-antiplasmin.

lumbar cistern

the CSF filled subarachnoid space extending from L1 "" S2. The lumbar cistern contains the cauda equina. - cauda equina consists of dorsal and ventral roots of L2-L5 nerve pairs, S1-S5 nerve pairs, and the C1 that exit BELOW the end of the spinal cord the nerves that compose the cauda equina innervate the pelvic organs and lower limbs to include motor innervation of the hips, knees, ankles, feet, internal anal sphincter and external anal sphincter. In addition, the cauda equina extends to sensory innervation of the perineum and, partially, parasympathetic innervation of the bladder

Asthma treatment

the aggressiveness of treatment depends on the frequency of asthma symptoms. Generally, an inhaled *β 2-adrenergic agonist* such as *albuterol* is used alone to treat mild disease and acute asthma attacks. Other medications are used to control symptoms and prevent acute attacks. These include: - inhaled corticosteroids - long acting inhaled β 2-adrenergic agonists (e.g., salmeterol - leukotriene modifiers (e.g., montelukast)

Causes of secondary hypertension

the most common is renal disease. This includes acute kidney injury and chronic kidney disease. Renal artery stenosis: Also, Cushing syndrome (high cortisol which mimics aldosterone). Drugs, such as cocaine, amphetamines and steroids also result in secondary hypertension.

prostate cancer diagnosis

• DRE—posterior lobe is palpable • Serum PSA levels • Transrectal U/S and biopsy

Hep B accidental seroconversion

the rate of seroconversion after accidental exposure to hepatitis B-infected blood is about 6% to 30%.

Esophageal webs

thin mucosal esophageal protrustion which protrudes into the esophageal lumen → solid food dysphagia (no liquid dysphagia).

Self recognition and tolerance

to function properly, t-cells must have 2 traits: 1) self-recognition- must be able to recognize own MHC proteins 2) self tolerance- must LACK reactivity to peptide fragments from your own proteins Loss of self tolerance leads to auto-immunity

Upper quadrantic anopia

transection of the Meyer's loops in the temporal lobe (contains input from the inferior retinal quadrants, which represent superior visual quadrants)

Homonymous Hemianopia

transection of the contralateral optic tract (contains fibers from ipsilateral temporal hemiretina and the contralateral nasal hemiretina)

Lower quadrantic anopia:

transection of the dorsal optic radiations in the parietal lobe (contains input from the superior retinal quadrants, which represent inferior visual field quadrants)

heart types of infarcts

transmural (usually complete occlusion of a coronary artery) subendocardial (due to prolonged ischemia, )

Treat h-pylori

triple therapy or quadruple therapy including antibiotics and proton pump inhibitors, and reinfection rates are minimal.

ABL mutation

tyrosine kinase signal transducer. abl:bcr (t9,22): translocation DEFINES chronic myeloid leukemia (CML).... also sometimes seen in acute lymphoblastic leukemia, and this type has poor prognosis

massive proteinurea in nephrotic syndrome

urinary loss of *>3.5 grams of protein per day* (!!!) This is the *hallmark*.

side effects of HRT

used mostly in early menopausal women DVT may increase breast cancer

HNP

usually on the posteolateral side because the posterior longitudinal ligament is incomplete laterally. The most common HNP sites are in the lower lumbar area. Sciatica, or irritation of the sciatic nerve, results from a L5-S1 disk herniation. • In a herniated disc or herniated nucleus pulposus (HNP), the annulus fibrosus undergoes degeneration and tears, allowing the nucleus pulposus to herniate out and impinge adjacent structures.

neutrophil margination

vasodilation slows blood flow in post-capillary venue, as as vasodilation occurs, cells marginate from center of vessel to periphery.

chemo sides

vomiting hair loss fatigue myelosupression

Hyperthyroid clinical features

weight loss w/ increased appetite - increased heat/sweating - tacycardia and increased CO -arrhythmia (especially a.fib, & in elderly). - tremor, anxiety, insomnia, hyperreflexia - lid lag (lagging of the UPPER eyelid on downward rotation of the eye) - exophthalmos (bulging eyeballs) - diarhea - Oligomenorrhea - bone resorption, hypercalcemia - HYPOcholesterolemia (↑ LDL receptor) - HYPERglycemia

atlanto-occipital joint

what allows you to nod your head and give the Ok. It is formed by the articulation between the atlas and the occipital condyles. The atlanto-occipital membranes limit excessive movements at this joint. "You OK with the Occipital "

Congestive heart failure

when the heart fails to pump properly, divided into either : - Left Congestive Heart Failure - Right Congestive heart failure

atlanto-dental joint

when you turn your head side to side to say no or deny. It is formed by the articulation between the atlas and the axis. The alar ligaments limit excessive movement at this joint. "You Deny with the Dental joints."

Gray vs white matter

white matter contains neuronal fibers gray matter consists of neuronal cell bodies- divided into dorsal, ventral and lateral horn

HIV tests

x: first test is ELISA. Confirm positives with Western blot. less ELISA is very sensitive → higher false-positive rate, so need confirmation PCR- viral load

Z line

zone of apposition of actin filaments belonging to two neighbouring sarcomeres (mediated by a protein called alpha-actinin

Medullary Carcinoma

~5% of thyroid cancer cases. - Parafollicular (C-cells) are malignant → ↑ calcitonin production, and thus hypocalcemia. - Cells stain positive for amyloid, calcium deposited in it. "Malignant cells in an amyloid stroma"

Hyperlipidemia and hypercholesterolemia in nephrotic syndrome

—as a result of ↑ hepatic synthetic activity, including synthesis of albumin and lipoprotein synthesis: ↑ VLDL → IDL → ↑ LDL ∴ ↑ cholesterol Think of it as we are *losing so much protein*, the liver *ramps up* synthesis of albumin and lipoproteins.

Menorrhagia

• - Bleeding more blood during menstrual period or for >7 days

thyrotoxicosis

• 1) Hypermetabolic state (e.g., ↑ Na/K ATPase activity): due to ↑ T4 and T3 • 2) SNS (sympathetic nervous system) overactivity: ↑ T4 and T3 → ↑ synthesis of β adrenergic receptors → ↑ β adrenergic tone

first trimester bleeding

• 4 Major sources: • Ectopic pregnancy **Most Serious** • Miscarriage (threatened, inevitable, incomplete, complete) **Most Common** • Implantation of the pregnancy • Cervical, vaginal or uterine pathology (e.g. Polyps, inflammation/infection, trophoblastic disease).

Polycythemia

↑ Hct, Hb, and RBC count. Usually due to chronic hypoxia.

Pulmonary embolism labs

↑ physiologic AND anatomic dead space. → V/Q mismatch at areas other than site of embolus. - ↑ A-a gradient. D-Dimer: this important lab test is used in the evaluation of a potential PE. A negative D-Dimer is a good prognostic sign that a PE is not present. A high level after treatment may be used to assess for the risk of recurrent DVT/PE.