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BASIC STRUCTURE AND PROMINENT FUNCTIONS OF VERTEBRATE INTEGUMENT INTRODUCTION The integument or the outer cover of the body is commonly referred to as the skin. Together with its derivatives it makes up the integumentary system. It is continuous with the mucous membrane lining the mouth, eyelids, nostrils, rectum and the openings of the urino-genital ducts. The skin functions primarily to cover and protect the tissues lying beneath it. In other words, it forms the external protective covering of an animal. Forms interface between organism and external environment. Part that the predator sees first, and which offers the first line of defense. Abundantly supplied with sensory nerve endings, which are affected by environmental stimuli and play an important role in communication. General metabolism of the body, temperature regulation and water loss. Character of the skin and its derivatives shows variation in different regions of the body, in different individuals, in the same individual as age advances and in different groups of vertebrates. The type of environment whether aquatic or terrestrial is of importance in connection with these variations. The evolution of vertebrate integument is correlated with the transition of vertebrates from an aquatic to a terrestrial environment. Nevertheless, basic similarities exist in the integument of all vertebrates. INTEGUMENT PROPER In Annelids, Arthropods, integument consists of single layer of cells, the EPIDERMIS, together with an outer non-cellular CUTICLE, secreted by the cells. Annelids have a body covered with an external thin collagenous cuticle (never shed or molted). In Arthropods, the chitinous and rigid cuticle makes up the exoskeleton. Periodic shedding of this cuticle is termed Ecdysis. THE VERTEBRATE SKIN DIFFERS FROM INVERTEBRATE SKIN TWO LAYERS – Outer epidermis derived from ectoderm Inner dermis or corium of mesodermal origin. The relative amount of the two layers varies with the environment. EPIDERMIS – the epidermis is made of stratified epithelium (several layers of columnar epithelium cells). These cells are held together tightly by minute intercellular bridges found on the surface of cells. The innermost layer is stratum Malpighii or stratum germinativum placed over a thin basement membrane. These cells divide constantly to produce new cells. Move upwards, tend to become flattened, protoplasm becomes horny (keratinisation). In fishes and amphibians, this keratinised layer forms a cuticle, but in amniotes, it forms stratum corneum, of hard, horny, flat, cornified cells made largely of keratin, which is tough, waterproof and insoluble protein. It affords protection against mechanical injuries, fungal and bacterial attacks and prevents desiccation. In many Tetrapoda, this layer is shed periodically in pieces or all at once. No stratum corneum in cyclostomes and fishes (since they are fully aquatic) here the epidermis has mucous glands, secreting mucus to keep the skin slimy and protects it from bacteria. The epidermis has no blood vessels and is nourished by capillaries in the dermis. The epidermis rests on a thin basement membrane which separates it from the dermis Dermis has an outer loose layer and inner dense layer Made up of dense connective tissue having cells, muscles, blood vessels, lymph vessels, collagen and elastic fibres, and nerves. Amphibians and reptiles -collagen fibres at right angles in three planes Birds and mammals, they have an irregular arrangement. Substances pass by diffusion from the dermis to the epidermis. Skin contains pigment, if present in epidermis, it occurs as a diffuse substance or as granules. If in dermis, then in the form of granules in special branching cells called chromatophores. The pigment can either collect as a central ball making the skin lighter or spread out into all the branches making the skin darker, thus, chromatophores bring about colour variations. Chromatophores are of many kinds, Melanophores that contain brown to black pigment Lipophores or xanthophores which contain yellow red fatty pigments Iridocytes or guanophores contain crystals of guanine which reflect light. Under dermis, the skin has subcutaneous loose areolar tissue which separates the skin from the underlying muscles, it may contain fat and muscles, especially in mammals. Integument of Anamnia shows a decrease in thickness and also a decrease in the degree of ossification. These are of advantage in allowing greater mobility and in amphibians, they permit respiration by the skin. But in Amniota, the skin becomes progressively thicker to prevent loss of water and to retain body heat. STRUCTURE OF INTEGUMENT IN CYCLOSTOMATA Epidermis is multi-layered (stratified) but has no keratin. It has three types of unicellular gland cells: mucus glands (secrete mucus), club cells (scab-forming cells) and granular cells (unknown function). Below epidermis is the cutis formed of collagen and elastin fibres. Star- shaped pigment cells are also present in the cutis. STRUCTURE OF INTEGUMENT IN PISCES The epidermis has several layers of simple and thin cells, but there is no dead stratum corneum. The outermost cells are nucleated and living. The stratum Malpighii replenishes the outer layers of cells which have some keratin. Unicellular goblet or mucous gland cells are found in the epidermis, as in all aquatic animals. The mucous makes the skin slimy reducing friction between the body surface and water, protects the skin from bacteria and fungi and assists in the control of osmosis. Multicellular epidermal glands like poison glands and light producing organs may also be found. The epidermis rests on a delicate basement membrane. The dermis contains connective tissue, smooth muscles, blood vessels, nerves, lymph vessels and collagen fibres. The connective tissue fibres are generally not arranged at right angles but run parallel to the surface. Scales are embedded in the dermis and projected above the epidermal surface. The colours of fishes are due to chromatophores and iridocytes. STRUCTURE OF INTEGUMENT IN AMPHIBIA: The epidermis has several layers of cells, six to eight cells in thickness and is divisible into three layers: stratum corneum, stratum germinativum and a basal portion in contact with the basement membrane. The outermost layer is a stratum corneum, made of flattened, highly keratinised cells. Such a dead layer appears first in amphibians and is best formed in those which spend a considerable time on land. The stratum corneum is an adaptation to terrestrial life (protects body and prevents excessive loss of moisture). In ecdysis, stratum corneum is cast off in fragments or as a whole in some. (moulting / desquamation i.e., removal of unicellular sheet of stratum corneum). The dermis is relatively thin in amphibians, it is made of two layers - upper loose stratum spongiosum and a lower dense and compact stratum compactum. Connective tissue fibres run both vertically and horizontally. Blood vessels, lymph spaces, glands and nerves are abundant in the stratum spongiosum. There are two kinds of glands, multicellular mucous glands and poison glands in the dermis, but they are derivatives of the epidermis. Mucous gland produces mucus (slimy protective covering, helps in respiration). Amphibian skin is an important organ of respiration. Poison glands produce a mild but unpleasant poison which is protective. In the upper part of the dermis are chromatophores. (melanophores and lipophores) Ability of the skin for changing colour to blend with the environment is well developed. INTEGUMENT IN REPTILIA. The integument is thick and dry, it prevents any loss of water, it has almost no glands. The only glands present are scent glands for sexual activity. The epidermis has a well-developed stratum corneum well adapted to terrestrial life. The horny scales of reptiles are derived from this layer. Ecdysis is necessary to remove dead outer layers, hence scales are shed periodically in fragments or cast in a single slough as in snakes and some lizards Scales often form spines or crests. Below the epidermal scales are dermal bony plates or osteoderms in tortoises, crocodiles and some lizards (Heloderma). The dermis is thick and has an upper layer and a lower layer, upper layer has abundance of chromatophores in snakes and lizards. Lower layer has bundles of connective tissue in which collagen fibres lie at right angles. Leather of high commercial value can be prepared from the skin of many reptiles like lizards, snakes and crocodiles. Many lizards and snakes have elaborate colour patterns, they may be for concealment or as warning colours. There is marked colour change in certain lizards such as chameleon, the colour may change with the environment for concealment or it may change in courtship or threat. The ability of chameleons and some other animals to change colour is known as metachrosis. (metachromatism) In Calotes, chromatophores are controlled by the posterior lobe of pituitary whereas in chameleons they are controlled by the Autonomic Nervous System. INTEGUMENT IN BIRDS Thin, loose, dry and devoid of glands. There is only a uropygial gland at the base of the tail, its oil is used for preening (to clean and tidy its feathers with its beak) and waterproofing the feathers (aquatic birds) Epidermis is delicate except on shanks and feet where it is thick and forms epidermal scales. The rest of the body has a protective covering of epidermal feathers. The keratin producing powers of the epidermis are devoted to producing feathers and scales. The dermis is thin and has interlacing connective tissue fibres, abundant muscle fibres for moving feathers, blood vessels and nerves. The dermis has an upper and lower compact layer, between which is a vascular layer, the dermis also contains fat cells. The skin has no chromatophores. Pigment is found only in feathers and scales. Colour patterns in birds are vivid (concealment, recognition and sexual stimulation) Colours are produced partly by pigments and partly by reflection and refraction from the surface of the feathers. INTEGUMENT IN MAMMALS Skin is elastic and waterproof, much thicker than in other animals, especially the dermis is very thick and is used in making leather. Epidermis is thickest in mammals. Outer stratum corneum containing keratin, cells not dead as believed before. Below this is stratum lucidum (barrier layer), chemical called eleidin Below this stratum granulosum, darkly staining granules of keratohyalin Below this is stratum spinosum whose cells are held together by spiny intercellular bridges. Lastly stratum germinativum which rests on a basement membrane Dermis is best developed in mammals. Upper layer is papillary layer made up of elastic and collagen fibres with capillaries in-between, thrown into folds called dermal papillae, especially in areas of friction Greater lower part of dermis is reticular layer, having elastic and collagen fibres. In both layers there are blood vessels, nerves smooth muscles, certain glands tactile corpuscles and connective tissue fibres in all directions. Below dermis the subcutaneous tissue contains a layer of fat cells forming adipose tissue In the lowest layer of epidermis there are pigment granules, no pigment bearing chromatophores in mammaIs (in man, branching dendritic cells or melanoblasts) FUNCTIONS OF THE INTEGUMENT ▪ PROTECTION ▪ TEMPERATURE CONTROL ▪ FOOD STORAGE ▪ SECRETION ▪ EXCRETION ▪ SENSATION ▪ RESPIRATION ▪ LOCOMOTION ▪ DERMAL ENDOSKELETON ▪ SEXUAL SELECTION 1. Protection: The integument forms a covering of the body and is protective. It protects the body against entry of foreign bodies and against mechanical injuries. It protects the tissues against excessive loss of moisture, this is very important because both aquatic and terrestrial animals are dependent upon water in their bodies for various metabolic activities. The integument forms protective derivatives, such as scales, bony plates, layer of fat, feathers and hair which reduce the effect of injurious contacts. In some animals the skin shows protective colouration which makes the animals resemble their environment, thus, making them almost invisible to their enemies. Poison glands of toads, slippery skin of aquatic animals and an armour of spines of some mammals are protective devices of the integument. The skin forms a covering which prevents the passage of water and solutes in one of the following ways: (a) By formation of cuticle in Protochordata and embryos of fishes and amphibians, (b) By secreting a coat of mucus in fishes and aquatic amphibians, and (c) By formation of keratin layers in the epidermis of tetrapoda. Keratin is formed from the cytoplasm of degenerating cells of the epidermis which finally form a layer of horny stratum corneum. 2. Temperature Control: Heat is produced constantly by oxidation of food stuffs in tissues. This heat is distributed evenly by the circulating blood. The body heat is lost constantly with expired breath, with faeces and urine, and from the surface of the skin. The integument regulates heat and maintains a constant temperature in endothermal animals. In birds the heat is regulated by adjustment of feathers which retain a warm blanket of air, when feathers are held close to the body, they remove warm air and body cooled, when feathers are fluffed out, they keep the warm air enclosed. In mammals, constant evaporation of sweat regulates the body heat. In cold weather contraction of skin’s blood capillaries reduces the loss of body heat. In some animals, fat in the skin prevents loss of heat because it is a non-conductor of heat. 3. Food Storage: The skin stores fat in its layers as reserve food material which is used for nourishment in times of need. In whales and seals the fat of the skin forms a thick layer, called blubber which is not only reserve food but also maintains the body temperature. 4. Secretion: The skin acts as an organ of secretion. Glands of the skin are secretory. In aquatic forms there are secretory mucous glands whose secretions keep the skin moist and slippery. In mammals, sebaceous glands secrete oil which lubricates the skin and hairs. Mammary glands produce milk for nourishment of the young. In birds uropygial glands secrete oil for preening the feathers. Odours of scent glands attract the opposite sex. Lacrymal glands’ secretion wash the conjunctiva of eyeball in mammals. Ear wax (cerumen) secreted by the glands of auditory meatus greases the eardrums and avoids insects to enter the canal. 5. Excretion: The integument acts as an organ of excretion. Shedding of the corneal layer during ecdysis removes some waste substances. In mammals metabolic waste (salts, urea and water) is removed from the blood by means of sweat. Chloride secreting cells are found in gills of marine fishes. 6. Sensation: The skin is an important sense organ because it has various kinds of tactile cells and corpuscles which are sensory to touch, temperature changes, heat, cold, pressure and pain. 7. Respiration: In amphibians, the moist skin acts as an organ of respiration, in frogs the respiratory function of the skin is greater than that of the lungs. 8. Locomotion: Derivatives of the integument bring about locomotion in some animals, such as the fins of fishes aid in locomotion in water, the web of skin in the feet of frogs and aquatic birds aid in swimming, feathers of the wings and tail of birds are used for flying, and extensions of the integument forming “wings” of flying lizards, extinct pterodactyls, flying squirrels and bats. 9. Dermal Endoskeleton: The skin contributes to the endoskeleton. It forms the dermal bones of vertebrates and also forms parts of the teeth. Endoskeleton of head protects the brain and sense organs. In the body it protects the soft, tender viscera. 10. Sexual Selection: The skin acts as an organ of sexual selection. It provides the feathers of birds which often have brilliant colours which are for sexual attraction. Some integumentary glands of mammals produce odours far attracting the opposite sex. Antlers of male deer distinguish it from female. Besides the above functions, mammalian skin synthesizes the vitamin D with the help of Sebum of sebaceous glands. Brood pouches beneath skin in some fishes and amphibians protect unhatched eggs. Nasal glands of tetrapods, keep the nostrils free of dirt and water. Skin also has the power of absorption of oils, ointments, etc
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Cardiovascular System - Detailed Summary 1. Functions of the Cardiovascular System • The cardiovascular system is a closed system consisting of the heart and blood vessels. • Main functions: • Transport oxygen, nutrients, hormones, and waste. • Maintain blood pressure and circulation. • Aid in immune function (through WBCs in blood). 2. Anatomy of the Heart • Location: Thoracic cavity, between the lungs, within the mediastinum. • Size: About the size of a fist. • Orientation: • Apex: Points toward the left hip (bottom). • Base: Directed toward the right shoulder (top, where large blood vessels attach). Heart Layers (Inside to Outside) 1. Endocardium – Inner lining of the heart, smooth to prevent clotting. 2. Myocardium – Thick muscular layer responsible for contraction. 3. Epicardium (Visceral Pericardium) – Outer covering of the heart. • Pericardium: A double-walled sac surrounding the heart. • Parietal Pericardium: Outer layer. • Visceral Pericardium: Inner layer (epicardium). • Pericardial Fluid: Lubricates and reduces friction during heartbeats. 3. Chambers of the Heart The heart has four chambers: • Atria (Right & Left): Upper receiving chambers. • Ventricles (Right & Left): Lower pumping chambers. • Right Side of the Heart: Pumps deoxygenated blood to the lungs (Pulmonary Circulation). • Left Side of the Heart: Pumps oxygenated blood to the body (Systemic Circulation). 4. Heart Valves Valves prevent backflow of blood: 1. Atrioventricular (AV) Valves – Between atria and ventricles: • Right AV Valve: Tricuspid Valve • Left AV Valve: Bicuspid (Mitral) Valve 2. Semilunar Valves – Between ventricles and arteries: • Pulmonary Semilunar Valve: Right ventricle → Pulmonary artery • Aortic Semilunar Valve: Left ventricle → Aorta • Chordae Tendineae (“Heart Strings”) anchor AV valves to prevent them from inverting. 5. Blood Flow Through the Heart 1. Deoxygenated Blood Pathway (Blue): • Superior/Inferior Vena Cava → Right Atrium → Tricuspid Valve → Right Ventricle → Pulmonary Semilunar Valve → Pulmonary Artery → Lungs 2. Oxygenated Blood Pathway (Red): • Lungs → Pulmonary Veins → Left Atrium → Bicuspid Valve → Left Ventricle → Aortic Semilunar Valve → Aorta → Body 6. Electrical Conduction System (Intrinsic Conduction System) The heart has automaticity (can contract on its own). • Sinoatrial (SA) Node (“Pacemaker”) – Sets the heart’s rhythm (~75 bpm). • Atrioventricular (AV) Node – Delays impulse so atria can contract first. • AV Bundle (Bundle of His) – Carries signal to ventricles. • Purkinje Fibers – Cause ventricles to contract. Disruptions in this system can cause arrhythmias (irregular heartbeats). 7. Cardiac Cycle (Heartbeat) Each cycle consists of: 1. Atrial Systole – Atria contract, pushing blood into ventricles. 2. Ventricular Systole – Ventricles contract, pumping blood to the lungs/body. 3. Diastole – Heart relaxes and fills with blood. • Heart Sounds: • “Lub” – Closing of AV valves during ventricular contraction. • “Dub” – Closing of semilunar valves during ventricular relaxation. 8. Cardiac Output (CO) • Definition: The amount of blood pumped by each ventricle per minute. • Formula: • CO = Heart Rate (HR) × Stroke Volume (SV) • Average CO = 5.25 L/min Factors affecting CO: • Sympathetic nervous system → Increases HR (exercise, stress) • Parasympathetic nervous system → Decreases HR (rest, sleep) • Hormones (epinephrine, thyroxine) → Increase HR 9. Blood Vessels & Circulation • Arteries: Carry oxygenated blood away from the heart (except pulmonary artery). • Veins: Carry deoxygenated blood to the heart (except pulmonary vein). • Capillaries: Tiny vessels for gas/nutrient exchange. Blood Vessel Structure 1. Tunica Intima – Inner layer, smooth to reduce friction. 2. Tunica Media – Middle layer, made of smooth muscle (controls blood pressure). 3. Tunica Externa – Outer layer for support. 10. Major Circulatory Routes • Pulmonary Circulation: Right ventricle → Lungs → Left atrium. • Systemic Circulation: Left ventricle → Body → Right atrium. Special Circulations: • Hepatic Portal Circulation: Blood from digestive organs goes through the liver before reaching the heart. • Fetal Circulation: Blood bypasses the lungs using special shunts (foramen ovale, ductus arteriosus). 11. Blood Pressure & Disorders • Blood Pressure (BP): The force of blood against vessel walls. • Normal BP: ~ 120/80 mmHg • Hypertension (High BP): >140/90 mmHg – Can damage arteries. • Hypotension (Low BP): <90/60 mmHg – Can cause dizziness or shock. Factors affecting BP: • Cardiac Output (CO) • Blood Volume • Vessel Resistance (narrower arteries = higher BP) 12. Common Cardiovascular Disorders • Hypertension (High Blood Pressure): Can lead to stroke, heart attack. • Atherosclerosis: Hardening of arteries due to plaque buildup. • Myocardial Infarction (Heart Attack): Blockage in coronary artery cuts off oxygen. • Arrhythmia: Irregular heartbeats due to conduction system issues no
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Primary adrenal insufficiency = problem at level of adrenal glands Causes? Addison’s disease Pathophys? Autoimmune destruction of the adrenal glands Associated with hyperpigmentation POMC is precursor to both ACTH and MSH PAI → lack of negative feedback → high ACTH Lab findings? ACTH high Aldosterone low Destruction of zona glomerulosa Renin high Hypotension → RAAS activation Electrolytes Na+ low, K+ high CBC Eosinophils high Pathophys? Glucocorticoids → eosinophil apoptosis. Lack of glucocorticoids cause eosinophilia. Dx? Cosyntropin testing → no rise in cortisol Adrenal glands aren’t working, so no response to ACTH. Tx? prednisone/hydrocortisone/dexamethasone + fludrocortisone (mineralocorticoid) Stress-dose steroids for surgery, serious illness, etc. Secondary adrenal insufficiency = problem at level of pituitary, reduced ACTH release Causes? MC is prolonged steroid use → ACTH suppression Sheehan’s syndrome (infarction of pituitary) pregnancy Pituitary tumors (ACTH-producing tumor) Lab findings? ACTH low Anterior pituitary is being inhibited Aldosterone normal Zona glomerulosa under control of RAAS system Renin normal Electrolytes Na+ & K+ unaffected (Aldosterone levels are normal) CBC Neutrophilia due to demargination (if pt was recently taking steroids) Dx? Cosyntropin testing → rise in cortisol Adrenal gland is functional Tx? Glucocorticoids Do not need to replace mineralocorticoids since adrenals are functional and aldosterone is under RAAS control Stress-dose steroids for surgery, serious illness, etc. AI with a history of nuchal rigidity and purpuric skin lesions → Waterhouse-Friedrichson syndrome Pathophys? AI 2/2 hemorrhagic infarction of the adrenal glands in the context of Neisseria meningitidis infection Adrenal synthesis enzymes If the enzyme starts with 1 → HTN (high mineralocorticoids) and hypokalemia If the second # is 1 → virilization (high androgens) E.g. 11-beta hydroxylase deficiency → HTN & virilization E.g. 21 hydroxylase deficiency → virilization only E.g. 17-alpha hydroxylase deficiency → HTN only B12 deficiency Where does B12 come from? Animal products VS folic from plants Physiology R factor in saliva binds to B12 and protects it from acidity in the stomach. R factor protector -B12 travels to the duodenum. Parietal cells produce intrinsic factor, which travels to the duodenum. Pancreatic enzymes cleave B12 from R factor and B12 then binds IF. B12-IF complex is reabsorbed in the terminal ileum Reabsorption where? Terminal ileum Causes of B12 deficiency Extreme vegan Pernicious anemia Pancreatic enzyme deficiency Cystic Fibrosis Can’t cleave B12 from R factor Crohn’s Affects terminal ileum Lab markers Homocysteine HIGH MethlyManoicAcid HIGH Presentation? Megaloblastic anemia Subacute combined degeneration (of dorsal columns + lateral corticospinal tract) Peripheral neuropathy Dx of pernicious anemia? anti-IF Ab Folate deficiency Where does folate come from? Leafy things Causes of folate deficiency Poor diet (e.g. alcoholics, elderly) Phenytoin Lab markers Homocysteine HIGH MMA normal Presentation? Megaloblastic anemia Prophylaxis in HIV+ patients CD4 < 200 → PCP TMP-SMX, inhaled pentamidine, dapsone, atovaquone CD4 < 100 → Toxoplasm Treat: TMP-SMX CD4 < 50 → MAC Treat: Azithromycin If live in endemic area, CD4 < 250 → Coccidioides Immitis E.g. Arizona, Nevada, Texas, California Treat: Itraconazole If live in endemic area, CD4 < 150 → Histoplasma Capsulatum E.g. Kentucky, Ohio, Missouri Treat: Itraconazole Diabetes insipidus Dx? Water deprivation test Measure serum osmolality & urine osmolality Deprive pt of water Remeasure serum osmolality & urine osmolality If urine osmolality doesn’t go up → suspect DI Central DI → deficiency of ADH Pathophys? Supraoptic nucleus not making enough ADH Dx? Give desmopressin → urine osmolality increases significantly Nephrogenic DI → kidneys are not responding to ADH Dx? Give desmopressin → urine osmolality doesn’t change much Tx? Hydrochlorothiazide Unless 2/2 lithium, use amiloride or triametere Causes? Lithium SSRIs Carbamazepine Demeclocycline Tx of normovolemic hypernatremia? D5W to correct free water deficit Divine says NS, but most other resources I found said correct free water deficit Tx of hypovolemic hypernatremia? Give NS first until normal volume, then give D5W Consequence of correcting hypernatremia too rapidly? Cerebral edema Osteoarthritis Presentation? Old person with joint pain that gets worse throughout the day Risk Factr? Obesity vs decreases osteoporosis Imaging findings? Joint space narrowing Subchondral sclerosis Subchondral cysts Osteophytes Arthrocentesis findings? <2000 cells Tx? 1st line acetaminophen 2nd line NSAID (e.g. naproxen) 3rd line joint replacement surgery Returned from a business conference 1 week ago + Fever + Nonproductive cough + Abdominal pain + Hyponatremia → Legionella Dx? Urine antigen Tx? FQ or macrolide MaCroLide mnemonic = Mycoplasma, Chlamydia, Legionella What are the common causes of atypical PNA? Mycoplasma, Legionella, Chlamydia MC cause? Mycoplasma CXR findings? Interstitial infiltrates HY associations C. Psittaci → birds C. Burnetii → cows, goats, sheet Mycoplasma → college student w/ walking pneumonia Midsystolic click heard best at the apex. → mitral valve prolapse “Stenosnap & Proclick” Risk Factor? Connective tissue disease Marfarn Ehlers-Danlos ADPKD bilateral renal masses Classic demographic? Young woman psychiatric Pathophys? Myxomatous degeneration MVP vs aortic dissection: cystic medial necrosis Exam maneuvers Anything that increase amount of blood in LV → murmur softer Increase preload Increase afterload Anything that decreases amount of blood in LV → murmur louder Dx? Echo Scaly, itchy skin with yellowish crusting in the winter. → seborrheic dermatitis Tx? Topical antifungals e.g. ketoconazole or selenium sulfide shampoo Classic disease distribution? Hair → e.g. cradle cap Eyebrows Episodic/intermittent HTN + HA → pheochromocytoma Genetic disease associations MEN2A MEN2B VHL in brain (hemangioma) NF-1 growth in skin Pathophys? Catecholamine-secreting tumor Location? Adrenal medulla Posterior mediastinum Organ of Zuckerkandl (chromaffin cells along the aorta) Dx? 1st step: urine metanephrines If elevated → CT abdomen If nothing found on CT → MIBG scan Tx? Alpha blocker (e.g. phenoxybenzamine, phenotaline) THEN beta blocker Most common cause of a Lower GI Bleed in the elderly → diverticulosis Dx? Colonoscopy or barium enema Recall that you acutely do a CT scan for diverticulitis, then 6 weeks later colonoscopy to r/o cancer Ppx? Eat fiber Megaloblastic anemias Blood smear findings? Hypersegmented neutrophils MCV > 100 Classic patient demographic with folate deficiency? Alcoholics Elderly person with poor nutrition Folate synthesis inhibitors Pt with molar pregnancy → methotrexate Pulmonary issue? Pulmonary fibrosis HIV+ pt with ring-enhancing lesions → pyrimethamine-sulfadiazine Pyrimethamine inhibits DHFR AIDS pt on ppx for toxo → TMP-SMX TMP inhibits DHFR Use of leucovorin? Rescue bone marrow in setting of methotrexate toxicity Mechanism? Folinic acid analog CMV presentations Esophagitis → linear ulcers Colitis → post-transplant pt Retinitis → HIV pt with CD4 < 50 Congenital CMV → periventricular calcifications + hearing loss calcifications elsewhere → toxo Histology? Owl’s eye intranuclear inclusions Tx? Gancicyclovir Resistance? UL97 kinase mutation Tx for resistance? foscarnet CD4 < 200 + severe peripheral edema + frothy urine. → FSGS in HIV pt Variant classic in HIV+ pts? Collapsing variant Tx? Steroids + cyclophosphamide + ACE-I Indinavir AE? Kidney stones triad of fever, rash, and eosinophiluria → acute interstitial nephritis Drugs cause? Penicillins Tx? Stop the drug! Can add steroids if severe Vitamin D metabolism Liver converts Vit D to calcidiol (25OH-Vit D). Calcidiol goes to kidney. Alpha-1 hydroxylase converts calcidiol to calcitriol (1,25-OH Vit D). Common causes of Vitamin D deficiency CKD → 1-alpha hydroxyalse deficiency Liver disease → can’t make calcidiol CF → malabsorption Crohn’s → malabsorption Osteomalacia vs Rickets Osteomalacia in adults Rickets in kids Tx? Calcium + vit D Lab findings? Ca++ low Phos low Low in liver disease High in kidney disease (kidneys can’t get rid of phos) PTH high (2ary hyperpara) vs liver dx PTH low Alk phos Aspiration pneumonia Risk Factor? Alcoholism Dementia Neuromuscular problems (e.g. MG, ALS) Bugs? Anaerobes foul smelling Bacteroides FUsobacterium Peptostreptococcus Klebsiella → currant jelly sputum alcoholic Tx? Clindamycin CURB-65 criteria Purpose? Who to admit Cutoff? 2+ → hospitalize C = confusion U = uremia (BUN > 20) R = RR > 30 B = BP < 90/60 Age > 65 Drugs commonly used in PNA treatment Ceftriaxone Levofloxacin fluoroquinolone Macrolides - great for atypical PNA Pharmacological management of pulmonary arterial HTN Endothelin antagonists Bosentan ambrisentan PDE-5 inhibitors Sildenafil Tadalafil Prostacyclin analogs Iloprost Epoprostenol Treprostinil Causes? Young female → idiopathic PAH Mutation? BMPR2 55 yo F presents with a 5 week history of a rash on her forehead. PE reveals scaly macules with a sandpaper texture. → actinic keratosis Risk Factor? Sun exposure Tx? Topical 5-FU Possible dangerous sequelae? Squamous cell carcinoma Most likely disease sequelae? Resolution 1ary hyperparathyroidism 2ary hyperparathyroidism 3ary hyperparathyroidism Autonomous PTH production Causes? Adenoma Parathyroid hyperplasia PTH high Ca++ high Phos low Low Ca++ → PTH production Causes? CKD PTH high Ca++ low Phos high PTH production despite normalized of Ca++ levels Causes? CKD s/p transplant PTH high Ca++ high Phos low Tx? Parathyroidectomy (remove 3.5 glands) Cinacalcet (CSR modulator) Hypercalcemia Presentation? bones, stones, groans, psychic overtones Tx? 1st step: Normal Saline Hypercalcemia of malignancy → bisphosphonates EKG finding? Shortened QT Periumbilical pain that migrates to the right lower quadrant. → appendicitis PE findings? McBurney’s point tenderness Psoas sign (flex hip pain) Obturator sign (pain with internal rotation of hip) Rovsing’s sign (palpation of LLQ → pain in RLQ) Dx? CT scan Pregnant → US Kid → US Tx? Surgery Classic drug and viral causes of aplastic anemia. Drugs? Carbamazepine Chloramphenicol Viral? Parvovirus B19 (single stranded DNA virus) Fanconi anemia Pathophys? Problems with DNA repair Fanconi anemia vs Fanconi syndrome Fanconi anemia → cytopenias + thumb anomalies + short stature + cafe-au-lait spots Fanconi syndrome → type 2 RTA (proximal) CD4 count of 94 + MRI revealing ring enhancing lesions in the cortex → toxoplasmosis Tx? Pyrimethamine-sulfadiazine Rescue agent for pt who becomes leukopenic with treatment? leucovorin Who should get steroids? Increased ICP For PCP pneumonia: O2 sat < 92 PaO2 < 70 A-a gradient > 35 Ppx? TMP-SMX for CD4 < 100 Congenital toxo Hydrocephalus Chorioretinitis Intracranial calcifications Classic methods of transmission? handling cat litter Lupus nephritis Associated autoantibody? anti-dsDNA Classic “immunologic” description? “Full house” pattern Tx? Steroids + cyclophosphamide Osteoporosis Screening population? women > 65 Screening modality? DEXA scan Dx? T-score < -2.5 Risk Factor? Postmenopauseal Low BMI Smoking Alcohol Preventive strategies? Weight bearing exercise Smoking cessation Reduce alcohol consumption Tx? 1st line: bisphosphonates + Ca/Vit D supplementation Raloxifene (SERM) Agonist in bone Blocker Antagonist in breast Classic locations of osteoporotic fractures Vertebral compression fracture Hip fracture Name the PNA Red currant jelly sputum. → Klebsiella Rust colored sputum. → Strep pneumo PNA in an alcoholic. → Klebsiella Post viral PNA with a cavitary CXR lesion. → Staph aureus PNA in a patient that has chronically been on a ventilator. → Pseudomonas MC cause of Community Acquired Pneumonia. → Strep pneumo Pharmacological management of MRSA. Vancomycin Clindamycin Linezolid Ceftaroline (5th gen cephalosporin) Tigecycline, tertracycline Pharmacological management of Pseudomonas. Ceftazidime (only 3rd gen cephalosporin) Cefepime (4th gen cephalosporin) Pip-tazo Fluoroquinolones Carbapenems Aztreonam Aminoglycosides JVD and exercise intolerance in a patient with a recent history of an URI. → dilated cardiomyopathy 2/2 viral myocarditis MC cause? Coxsackie B VS Coxsackie A: Hand foot mouth dx Drug causes myocarditis Clozapine Anthracyclines Prevention? Dexrazoxane (iron chelator) Trastuzumab reversible tx for breast cancer Classic cause in a patient with recent history of travel to S. America? Chagas T. Cruzi Potential sequelae? Achalasia Dilated cardiomyopathy Megacolon (2/2 degeneration of myenteric plexus) Massive skin sloughing (45% BSA) in a patient that was recently started on a gout medication? TEN Dx? <10% BSA → SJS >30% BSA → TEN Tx? STOP the drug IVF Topical abx to prevention infection Tetany and a prolonged QT interval in a patient with recent surgical treatment of follicular thyroid carcinoma. → hypocalcemia due to removal of parathyroids Recurrent viral infections + QT prolongation + tetany → DiGeorge syndrome Pathophys? Failure of development of 3rd/4th pharyngeal pouches Trousseau and Chvostek signs. Trousseau → inflation of BP cuff causes carpopedal spasm Chvostek → taping on cheek causes facial muscle spasm Hypocalcemia that is refractory to repletion → consider hypomagnesemia Electrolyte/drug causes of prolonged QT intervals Electrolytes? Hypocalcemia Hypomagnesemia Hypokalemia Drugs? Macrolides FloroQunlones Haloperidol Ondensatron Methadone Hypoalbuminemia and Ca balance Hypoalbumenia → decrease in total body Ca++, no change in ionized Ca++ Drop of 1 in albumin → add 0.8 to Ca++ Abdominal pain radiating to the back → acute pancreatitis Causes? #1 = Gallstones #2 = Alcohol Hypertriglyceridemia Hypercalcemia Scorpion sting Handlebar injuries Lab markers? Lipase - most sensitive Amylase Physical exam signs in pancreatitis. Cullen’s sign = periumbilical ecchymosis Grey Turner sign = flank ecchymosis Tx? NPO + IVF + pain control Meperidine is a good agent because it doesn’t cause sphincter of Oddi spasms Management of gallstone pancreatitis Dx? US then ERCP Tx? DELAYED cholecystectomy What if the patient becomes severely hypoxic with a CXR revealing a “white out” lung? ARDS noncardiogenic pulm edema PCWP? <18 mmHg NORMAL 20 yo M with red urine in the morning + hepatic vein thrombosis + CBC findings of hemolytic anemia. → paroxysmal nocturnal hemoglobinuria Pathophys? Defect in GPI anchors, which attach CD55 and CD59 to cell (they prevent complement from destroying RBC) Sleep → hypoventilation → mild respiratory acidosis → activation of complement cascade Gene mutation? PIGA Dx? Flow cytometry Tx? Eculizumab (terminal complement inhibitor) Vaccine required? pnemococal Neisseria meningitidis Chronic diarrhea and malabsorption in a HIV+ patient + detection of acid fast oocysts in stool. → cryptosporidium parvum Acid-fast organisms Cryptosporidium TB MAC Nocardia Dx? Stool O&P Tx? Nitazoxanide Route of transmission? Contaminated water Muddy brown casts on urinalysis in a patient with recent CT contrast administration (or Gentamicin administration for a life threatening gram -ve infection) → Acute Tubular Necrosis Woman with morning joint stiffness > 1 hr → Rhematoid Arthritis. Antibodies? Rheum Factor (IgM against IgG) anti-CCP - more specific HLA? DR4 Pathophys? IgM constant region activates complement → inflammation → formation of pannus (hypertrophied synovium) → damage to cartilage and bone Caplan syndrome = RA + pneumoconiosis Felty syndrome = RA + neutropenia + splenomegaly (“RANS”) Classic hand/finger findings/distribution? MCP & PIP joints of hands (DIP joints spared) Imaging findings? Symmetric joint space narrowing Tx? Methotrexate (DMARDs) If no response → TNF alpha inhibitor (e.g. infliximab) Required testing prior to starting methotrexate? PFTs Required testing prior to starting infliximab? TB Hep B/Hep C Differentiating Strep pharyngitis from Infectious Mononucleosis LND distribution Anterior cervical → Strep Posterior cervical → Mono Disease onset Acute → Strep Over weeks → Mono Organ involvement Splenomegaly → Mono Pt with sore throat takes amoxicillin and gets rash → mono NOT allergic rxn! CENTOR criteria C = absence of Cough E = tonsillar Exudates N = nodes/anterior cervical lymphadenopathy T = temp (fever) OR <15 → +1 >=45 → -1 Using CENTOR score 0/1 → don’t test, don’t treat 2/3 → rapid antigen test Positive → treat Negative → throat culture 4/5 → treat empirically Tx of Strep pharyngitis? Amoxillcin If PCN allergic → azithromycin Potential sequelae of Strep pharyngitis RF - preventable with abx PSGN Endocarditis MC cause of endocarditis? IVDU Bug? Staph aureus Valve? tricuspid Prosthetic valve endocarditis Bug? Staph epidermidis Endocarditis after dental procedure? Viridans group streptococci Strep viridans, Strep mitis, Strep mutans, Strep sanguineous Patient with malar rash and echo showing vegetations on both sides of the mitral valve → Libman-Sacks endocarditis Presentation? Fever + night sweats + new murmur Splinter hemorrhages Roth spots (retinal hemorrhages) Painless Janeway lesions + painful Osler nodes (immune phenomenon) Dx? 1st step: blood cultures TEE Tx? Abx that include Staph aureus coverage (e.g. vancomycin) for WEEKS Bugs implicated in culture negative endocarditis HACEK H = haemophilus A = actinobacillus C = cardiobacterium E = eikenella K = kingella Coxiella burnetii Blood cultures in a patient with endocarditis reveal S. Bovis (or S. Gallolyticus bacteremia). NBS? Colonoscopy Who needs antibiotic prophylaxis? Hx endocarditis Prosthetic valve Unrepaired cyanotic congenital dz Heart transplant with valve dysfunction Erythematous salmon colored patch with silvery scale on the elbows and knees. → psoriasis Tx? Topical steroids If this patient presents with joint pain (especially in the fingers)? Psoriatic arthritis Imaging? Pencil-and-cup deformity Tx? NSAIDs T of 104 + tachycardia + new onset Afib in a patient with a history of Graves disease. → thyroid storm Lab findings? TSH low T3/T4 high Tx? 1st step: propranolol 2nd step: PTU Then: Prednisone Potassium iodide (Lugul’s solution) Wolff-Chaikoff effect → large amounts of iodine inhibit thyroid hormone synthesis Biopsy revealing tennis racket shaped structures in cells of immune origin. → Langerhans cell histiocytosis Electron microscopy? Birbeck granules (tennis rackets) Marker? S100 Small bowel obstruction in a HIV patient with purple macules on the face, arms, and lower extremities. → Kaposi’s sarcoma Bug? HHV8 Tx? HAART Pathophys of vascular lesions? Overexpression of VEGF Fever + rash + eosinophiluria 10 days after a patient started an antistaphylococcal penicillin. → acute interstitial nephritis Tx? STOP drug + steroids SLE SOAP BRAIN MD S = serositis O = oral ulcers A = arthritis P = photosensitivity B = blood disorders (cytopenias) R = renal A = ANA/anti-dsDNA I = immunologic N = neurologic findings M = malar rash D = discoid rash Type 2 vs 3 HSRs in lupus Type 2 → cytopenias Type 3 → all other manifestations Lupus Ab? ANA anti-dsDNA anti-Smith Lupus nephritis → full house pattern on IF Antiphospholipid antibody syndrome → recurrent pregnancy losses Pathophys? Thrombosis of the uteroplacental arteries. MC cause of death in lupus patients? What I’ve read recently: CV disease Per Divine: Treated → infection Untreated → renal dz Also 40x risk MI Endocarditis in lupus pt? Libman-Sacks endocarditis Neonatal 3rd degree heart block → neonatal lupus Maternal autoimmune dz? Sjogren’s SLE Ab? anti-SSA/anti-Ro anti-SSB/anti-La Tx? Steroids Cyclophosphamide Hydroxychloroquine → good for skin lesions Pulmonary abscesses Bugs? Staph Anaerobes Klebsiella RF? Alcoholism Elderly Post-viral pneumonia MC location of aspiration pneumonia? Superior segment of RLL Chest pain worsened by deep inspiration and relieved by sitting up in a patient with a recent MI or elevated creatinine or URI or RA/SLE. → pericarditis EKG findings? Diffuse ST elevations + PR depression PE finding? Friction rub (“scratchy sound on auscultation”) A few days after MI → fibrinous pericarditis Weeks after MI → Dressler’s Tx? NSAIDS Consider adding on colchicine Cardiac tamponade Beck’s triad = hypotension + JVD + muffled heart sounds EKG findings? Electrical alternans Type of shock? Obstructive cardiogenic (Amboss) CO low SVR high PCWP high Tx? Pericardiocentesis or pericardial Pearly lesion with telangiectasias on the ear in a farmer. → Basal Cell Carcinoma MC type skin cancer Location? Upper lip Dx? Biopsy Tx? Mohs surgery Cold intolerance in a 35 yo white F → hypothyroidism MC cause? Hashimoto’s Histology? lymphoid follicles w/ active germinal centers Lab findings? TSH high T3/T4 low Ab? anti-TPO Anti-thyroglobulin HLA? DR3/DR5 Tx? Levothyroxine Future complication? thyroid lymphoma Massive hematemesis in a patient with a history of chronic liver disease. → ruptured varices Pathophys? L gastric vein has anastomosis with azygos veins. Increased portal pressure → backward flow from L gastric veins to azygous vein (which empties into SVC). Acute tx? IVF + octreotide + ceftriaxone/cipro + EGD w/ ligation/banding Do NOT give a beta blocker for acute tx Prophalaxsis? Beta blocker + spironolactone Other manifestations of elevated portal pressures Caput medusa Internal hemorrhoids Tx for cirrhotic coagulopathies? FFP If uremia → give desmopressin Note: Desmopressin = ADH analog → so, it can cause AE of hyponatremia 2/2 SIADH Hemophilia A Pathophys? deficiency of factor 8 Inheritance? XLR Coag labs? Bleeding time normal PTT HIGH b/c clotting problem PT normal Hemophilia B Pathophys? deficiency of factor 9 Inheritance? XLR Coag labs? Bleeding time normal PTT HIGH PT normal Hemophilia C Pathophys? deficiency of factor 11 Inheritance? AR Coag labs? Bleeding time normal PTT HIGH PT normal Bernard Soulier Syndrome Pathophys? Deficiency of GpIb Coag labs? Bleeding time HIGH PTT normal PT normal Glanzmann Thrombasthenia Pathophys? Deficiency of GpIIbIIIa Coag labs? Bleeding time HIGH PTT normal PT normal Von Willebrand’s disease Pathophys? Deficiency of vWF Inheritance? AD Coag labs? Bleeding time HIGH PTT HIGH vWF is a protecting group for factor 8 PT normal ITP Pathophys? Ab against GpIIbIIIa Classic pt? Pt with SLE Tx? Observation Steroids IVIG Splenectomy TTP Pathophys? Deficiency in ADAMTS13 enzyme → cannot cleave vWF multimers → activation of platelets → thrombosis → thrombocytopenia Presentation? microangiopathic hemolytic anemia + thrombocytopenia + renal failure + fever + neurologic problems Tx? Plasma exchange transfusion****** HUS Bugs? Shigella or E. coli O157:H7 Presentation? Fever+ microangiopathic hemolytic anemia + thrombocytopenia + renal failure + neurologic Platelet deficiency vs coagulation factor bleeds Platelet deficiency → mucosal bleeds, petechiae, heavy menses Coag factor deficiency bleeds → hemarthrosis Why do patients with CKD develop coagulopathy? Uremia → platelet dysfunction Tx? Desmopressin Note: Desmopressin = ADH analog → so, it can cause AE of hyponatremia 2/2 SIADH Exercising caution with transfusion in patients with Bernard Soulier syndrome Do NOT give transfusion that includes platelets They can have an anaphylactic rxn to GpIb (since they don’t have GpIb) Oropharyngeal candidiasis. RF? HIV Chronic ICS use TNF inhibitor Micro finding? Germ tubes at 37 C Tx oral candidiasis? Nystatin swish-and-swallow Tx invasive candidiasis? Amphotericin B Prevention of Amphotericin B toxicity? Liposomal formulation Pleural effusions Light’s criteria (must meet all 3 to be considered transudative!) LDH < 2/3 ULN LOW Pleural LDH/serum LDH < 0.6 LOW Pleural protein/serum protein < 0.5 LOW Causes of transudative effusion CHF Cirrhosis Nephrotic syndrome Note: Per UW 2021: Mechanism of transudate effusion? Decreased pulmonary artery oncotic pressure, e.g. hypoalbuminemia in nephrotic syndrome Increased pulmonary capillary hydrostatic pressure, e.g. volume overload in heart failure Causes of exudative effusion Malignancy Cancer Parapneumonic effusion Tb Note: Per UW 2021: Mechanism of exudate effusion? Inflammatory increased in vascular permeability of membrane (increased flow of interstitial edema into pleural space) Unique cause of both transudative & exudative effusions? PE Classic Pleural Effusion findings? Decreased breath sounds Dullness to percussion Decreased tactile fremitus Tx? Chest tube Chylothorax = lymph in the pleural space Pathophys? Obstruction of thoracic duct or injury to the thoracic duct Pleural fluid findings? High Triglycerides Holosystolic murmur heard best at the apex with radiation to the axilla in a patient with a recent MI. → mitral regurg 2/2 papillary muscle rupture Dx? Echo Why widely split S2? Aortic valve is closing earlier (LV is emptying into both aorta & LA) Maneuvers that increase intensity Increase preload (putting more blood in that can be regurgitated) Increase afterload Decubitus ulcers RF? Elderly Paraplegic Fecal/urinary incontinence Poor nutrition Staging Stage 1 = non-blanchable erythema Tx? Repositioning q2hrs Stage 2 = loss of epidermis + partial loss of dermis Tx? Occlusive dressing superficial Stage 3 = involves entire dermis, extending to subQ fat Does NOT extend past fascia Tx? Surgical debridement Stage 4 = muscle/tendon/bose exposed Tx? Surgical debridement General tx strategies? Repositioning + good nutritional support Marjolin’s ulcer = non-healing wound that is actually squamous cell carcinoma T1DM Pathophys? Autoimmune destruction of pancreas Ab? anti-GAD 65 (glutamic acid decarboxylase) anti-IA2 (islet tyrosine phosphatase 2) Islet cell autoantibodies Insulin autoantibodies Dx? A1c > 6.5% (twice) Fasting BG >= 126 (twice) Oral glucose tolerance test >= 200 (twice) Sxs of DM + random glucose > 200 Tx? Long-acting insulin + mealtime insulin Long-acting Glargine Detemir Rapid-acting Lispro Aspart Glulisine 3 HY complications Nephropathy Retinopathy & cataracts Neuropathy Chronic DM care A1c q3 months Foot exam annually Eye exam annually Microalbumin:Cr ratio annually Nephroprotection in DM? ACE-I GI bleed algorithm 1st step: ABCs + 2 large-bore IVs + IVFs 2nd step: NG lavage Clear fluid → go deeper Blood → UGIB → upper endoscopy Bilious fluid → have ruled out UGIB → proceed to colonoscopy See source → intervene as needed See nothing → CT angiography for large bleed Tagged RBC scan for smaller bleed Antiplatelet Pharmacology Aspirin Mechanism? Irreversibly inhibits COX-1 and COX-2 Clopidogrel/ticlopidine = P2Y12 (ADP receptor) blockers Mechanism? Inhibit platelet activation Abciximab/eptifibatide/tirofiban = GpIIbIIIa receptor blockers Mechanism? Inhibit platelet aggregation Ristocetin cofactor assay Issues with adhesion step → abnormal result Abnormal ristocetin cofactor assays: Von Willebrand disease Bernard Soulier disease Normal ristocetin cofactor assay: Glanzmann Thrombasthenia Von Willebrand disease effects on PTT? Increased Pathophys? vWF is a protecting group for Factor 8. Treatment of VWD? Desmopressin Mechanism? Increases release of vWF from Weibel-Palade bodies of endothelial cells Note: Desmopressin = ADH analog → so, it can cause AE of hyponatremia 2/2 SIADH HSV1 vs HSV2. Oral herpes → HSV1 Genital herpes → HSV2 Dx? PCR (most up-to-date) Tzanck smear (outdated, not very sensitive, nonspecific) → intranuclear inclusions Brain area affected by HSV encephalitis? Temporal lobes CSF findings in HSV encephalitis? RBCs******* Tx herpes encephalitis? Acyclovir AE? Crystal nephropathy Can’t see, can’t pee, can’t climb a tree. → reactive arthritis HLA? B27 Classic bug? Chlamydia Tx? steroids Need abx? Only if ongoing infection Can’t see, can’t pee, can’t hear a bee → Alport syndrome Inheritance? X-linked dominant Tx of NG & CT NG → treat empirically for both → ceftriaxone + azithro/doxy CT → azithro/doxy Hypovolemic Septic Neurogenic Cardiogenic CO low PCWP low SVR high*** CO high PCWP normal SVR low Tx? norepi CO low SVR low CO low PCWP high*** SVR high*** Tx anaphylactic shock? epinephrine Melanomas ABCDE A = asymmetry B = irregular borders C = color variation D = diameter > 6 mm E = evolving Dx? Full-thickness biopsy Excisional for small lesions Punch for larger lesions Most important prognostic factor → Breslow depth DM pharmacology Lactic acidosis → metformin Decreases hepatic gluconeogenesis → metformin Hold before CT w/ contrast → metformin Weight gain → sulfonylureas & TZDs (-glitizones) Diarrhea → acarbose & migliton Inhibits disaccharidases (can’t reabsorb disaccharides) Recurrent UTIs → SGLT-2 inhibitors Weight loss → GLP-1 agonists (e.g. liraglutide, exenatide) & DPP4 inhibitors (-gliptins) Contraindicated in pt with HF → TZDs PPAR-gamma receptor found in kidney → water retention Contraindication in pt with MTC → GLP-1 agonists Biggest risk of hypoglycemia? Sulfonylureas RF esophageal adenocarcinoma Barrett’s esophagus RF esophageal squamous cell carcinoma Smoking Drinking Achalasia Location esophageal adenocarcinoma? Lower 1/3 Location esophageal squamous cell carcinoma? Upper 2/3 MC US? Adenocarcinoma MC worldwide? Squamous cell carcinoma Presentation? Dysphagia to solids → dysphagia to liquids Dx? EGD Staging? CT scan or esophageal US Factor V Leiden Pathophys? Resistance to protein C Dx? Activated Protein C resistance assay Patient needs super large doses of heparin to record any changes in PTT → AT-III deficiency Recall that heparin is a AT-III activator 35 yo with a hypercoagulable disorder that does not correct with mixing studies. → antiphospholipid antibody disorder Anaphylaxis in a patient with a long history of Hemophilia A → Ab against factor 8 that cause type 1 HSR with transfusion Hx of hemophilia, diagnosed 5 years ago. Before you would give them factor 8 concentrate and PTT would normalize. Now they’re requirizing larger doses of factor 8 to normalize PTT. → inhibitor formation (antibodies against clotting factors) Skin necrosis with Warfarin → protein C/S deficiency Prothrombin G20210 mutation → overproduction of factor II Rash in dermatomal distribution → VZV infection Contraindications to VZV vaccination? Pregnant woman Kid < 1 year Severe immunosuppression (e.g. HIV with CD4 < 200) Tx? Acyclovir If resistant, foscarnet Tzanck smear findings? Intranuclear inclusions Shingles vaccination guidelines? Adults over 60 #1 cause of ESRD in the US → DM nephropathy Histology? Kimmelsteil-Wilson nodules #2 cause of ESRD in the US → hypertensive nephropathy Pt with BP 240/150. How fast should you lower BP? 25% in first 24 hrs Drugs for hypertensive emergencies? Nicardipine Clevidipine Nitroprusside AE? Cyanide poisoning Tx? Amyl nitrate + thiosulfate OR hydroxocobalamin Labelol Renal protective medications in patients with DKD or hypertensive nephropathy? ACE-I Anemia + Cranial Nerve deficits + Thick bones + Carbonic Anhydrase 2 deficiency + Increased TRAP + Increased Alkaline Phosphatase. → osteopetrosis Pathophys? Carbonic anhydrase is defective → osteoclasts cannot produce acid to resorb bone Tx? IFN-gamma Osteoclasts are a specialized macrophage IFN-gamma is an activator of macrophages Clinical diagnostic criteria for Chronic Bronchitis Diagnostic criteria? 2 years 3 months/year of chronic cough PFT findings FEV1 low FEV1/FVC ratio low RV high TLC high Which PFT market can differentiate CB from emphysema? DLCO DLCO normal → CB DLCO low → emphysema ****** Tx acute exacerbation? Abx + bronchodilators + corticosteroids (“ABCs”) Prevention? Stop smoking! Afib #1 RF? Mitral stenosis #1 RF MS? Rheumatic fever #1 RF CAD and AAA: smoking #1 RF stroke and aortic dissection: HTN MC arrhythmia in hyperthyroidism → Afib MC site of ectopic foci in Afib → pulmonary veins EKG findings? “Irregularly irregular” + no P waves Location of emboli formation? LA appendage Who should be cardioverted back to sinus rhythm? New onset (<48 hrs) Afib Anticoagulated for 3 weeks + TEE negative for clot Afib that’s refractory to medical therapy Afib & HDUS Q on T phenomenon? Depolarization during T wave (repolarization) can cause QT prolongation → Torsades → death Prevention? SYNCHRONIZED cardioversion Tx? Rate control Beta blockers ND-CCB (e.g. verapamil, diltiazem) Rhythmic control Amiodarone Reducing stroke risk in Afib? Anticoagulation for CHA2DS2VASc score >= 2 Anticoagulation options Valvular cause (e.g. MS) → warfarin Any other cause → warfarin or NOAC (apixiban) Reversal of AC Warfarin → Vit K, four-factor PCC Heparin → protamine sulfate Dabigatran → idarucizumab Crusty, scaly, ulcerating lesion with heaped up borders → squamous cell carcinoma Classic location? Below Lower lip Precursor lesion? Actinic keratosis What if it arises in a scar or chronic wound? Marjolin ulcer Hypothermia + hypercapnia + non pitting edema + hyponatremia + HR of 35 + hypotension in a patient with a history of papillary thyroid cancer → myxedema coma Tx? Levothyroxine + steroids Lab findings? TSH high T3/T4 low LDL high Acute onset “dermatologic” breakout in a patient with a recent history of weight loss and epigastric pain. → Leser–Trélat sign associated with visceral malignancy pancreatic cancer Lymph node associations Supraclavicular → Virchow’s node Periumbilical → Sister Mary Joseph What are mets to the ovaries called? Kruckenberg tumor Classic bug associated with gastric cancer? H. pylori (MALToma) Classic histological finding in the diffuse type of gastric cancer? Signet ring cells RBCs without central pallor + elevated MCHC + anemia. → hereditary spherocytosis Inheritance? AD Pathophys? Deficiency of spectrin, ankyrin, or band 3.2 Intravascular or extravascular hemolysis? Extravascular (RBCs bound by IgG, attacked by splenic macrophages) Dx? Osmotic fragility test Eosin-5-maleimide Acidified glycerol lysis test Tx? Splenectomy Post-splenectomy preventative care? Strep pneumo Hinflue vaccine Neisseria Septic shock Hemodynamic parameters CO high SVR low PCWP normal MvO2 high Tx? IVF + norepi + broad-spectrum abx (cover MRSA + Pseudomonas) E.g. vanc + pip-tazo E.g
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Introduction to Tissues A. Histology=the study of tissues. B. Although studying tissues can be accomplished using a light microscope, studying cell parts often requires an electron microscope and the study of atoms and molecules can only be examined through special imaging techniques and experimental procedures. Types of Tissues A. Despite the fact the body is composed of trillions of cells, there are only about 200 different cell types. These cells in turn produce only four principle tissue types: 1. Epithelial tissues=covers exposed surfaces; lines internal passageways; and produces glandular secretions. 2. Connective tissues=fills internal spaces; provides structural support, and stores energy 3. Muscle tissues=contracts to produce active movements 4. Nervous tissue=conducts electrical impulses; detects, interprets, and responds to stimuli B. Relative contribution of the four tissue types to the overall weight of the adult body. C. Embryonic origins: There are three types of embryonic tissues from which all adult tissues are derived. a. Endoderm=gives rise to the functional linings of the digestive and respiratory tracts as well as to the associated accessory glands and organs (i.e. liver, stomach, pancreas, etc.) b. Mesoderm= gives rise to the components of the skeletal, muscular, and circulatory systems c. Ectoderm= gives rise to the epidermis of skin and all of the components of the nervous system D. Tissue Membranes 1. Mucous Membranes=composed of epithelial tissues. These membranes line body cavities that open to the exterior environment such as those of the digestive tract, respiratory tract, or urogenital tract. In all cases, these are "wet" or moist membranes because of the secretion of mucous. The moisture helps reduce friction and in many cases, facilitates absorption or secretion activities. 2. Serous Membranes=consists of a mesothelium supported by areolar tissue. These are never exposed or connected to the exterior. Serous membranes secrete transudate, or serous fluid. There are three serous membranes that line the ventral body cavity: a. Pleura=lines the chest cavity and surrounds the lungs. b. Pericardium=lines the pericardial cavity and surrounds the heart c. Peritoneum=lines the peritoneal cavity and lines the surfaces of the visceral organs 3. Cutaneous Membranes=made of stratified squamous and areolar tissue reinforced by dense irregular connective tissue. In contrast to mucous and serous membranes, cutaneous membranes are dry, relatively thick, and waterproof. 4. Synovial Membranes=line mobile joint cavities but do not cover the opposing joint surfaces. Secretes synovial fluid. Although the covering of the synovial membrane is often called an epithelium, it differs from true epithelia in four respects: it develops within a connective tissue, no basal lamina is present, gaps of up to 1 mm may separate adjacent cells, and the synovial fluid and capillaries in the underlying connective tissue are continuously exchanging fluid and solutes. Epithelial Tissues A. Functions of Epithelial Tissues 1. Epithelia provide physical protection. Epithelial tissues protect exposed and internal surfaces from abrasion, dehydration, and destruction by chemical or biological agents. 2. Epithelia control permeability. Any substance that enters or leaves the body has to cross an epithelial tissue. Some epithelia are relatively impermeable, whereas others are permeable to compounds as large as proteins. Most are capable of selective absorption or secretion. The epithelial barrier can be regulated and modified in response to various stimuli. For example, a callus forms on your hands when you do rough work for an extended period of time. 3. Epithelia provide sensation. Sensory nerves extensively innervate most epithelia. Specialize epithelial cells can detect changes in the environment and convey information about such changes to the nervous system. 4. Epithelial cells that produce secretions are called glands. Individual gland cells are often scattered among other cell types in an epithelium that may have many other functions. B. Location of Epithelial Tissues 1. Epithelia=forms sheets or layers of cells that line the body tubes, cavities, or coverings of the body surfaces. 2. Glands=formed of epithelial cells with secretory functions. Two types of glands are found in the human body: a. Endocrine glands=secrete hormones (or hormonal precursors) into the interstitial fluid or bloodstream. These glands are ductless. b. Exocrine glands=secretes non-hormonal substances (milk, wax, enzymes, oil, acids, etc.) onto external surfaces or internal passageways (ducts) that connect to the exterior. C. Characteristics of Epithelial Tissues 1. Polarity=epithelial cells possess two structurally and functionally different surfaces: a. Apical surface=free edge which faces the exterior of the body or the lumen of an internal space. b. Basal surface=attached surface which anchors the cells to adjacent tissues. 2. Supported by a basal lamina=also known as the basement membrane, is a complex structure produced by the basal surface of the epithelial cells and the underlying connective tissue. The underlying connective tissue is composed of two things: 3. Cellularity=epithelial cells are extensively interconnected so that they create an effective barrier that behaves as if it were a single cell. a. Occluding junctions=form a barrier that isolates the basolateral surfaces and deeper tissues from the contents of the lumen. At an occluding junction, the attachment is so tight that it prevents the passage of water and solutes between the cells. b. Adhesion belt=locks together the terminal webs of neighboring cells, strengthening the apical region and preventing distortion and leakage at the occluding junctions. It forms a continuous band that encircles cells and binds them together. c. Gap junctions=permits chemical communication that coordinates the activities of adjacent cells. At a gap junction, two cells are held together by interlocking junctional proteins called connexons which serve as channels that form a narrow passageway to let small molecules and ions to pass from cell to cell. d. Desmosomes=provides firm attachment between neighboring cells by interlocking their cytoskeletons. At a desmosome, the opposing plasma membranes are very strong and resist stretching and twisting. Hemidesmosomes attach the basal surface to the basement membrane. e. CAM=cell adhesion molecules; present in the adhesion belt and desmosomes; transmembrane proteins that bind to each other and to extracellular materials. 4. Avascular=epithelial tissues lack blood vessels; all nutrient and waste exchange occurs as a result of diffusion and osmosis from underlying tissues. 5. Highly innervated=epithelial tissues are supplied with many nerve endings 6. Regenerate rapidly=although the exact rate varies from one type of epithelia to another, most epithelial tissues regenerate within days (rather than weeks or years). D. Naming Epithelial Tissues 1. Almost all epithelial tissues possess a two part name where the first part of their name indicates their arrangement (number of layers) while the second part of their name indicates the shape of the cells. 2. Arrangement of epithelial tissues a. Simple=only one layer thick b. Stratified=more than one layer thick c. Pseudostratified= “false layers”; it looks like more than one layer but in fact its only one layer thick 3. Shape of epithelial cells a. Squamous=thin, flat, and somewhat irregular in shape. From the surface, they look like fried eggs lay side by side. In a sectional view, they look like a pancake with a pat of butter (indicating the nucleus). b. Cuboidal=are about as wide as they are tall; resemble hexagonal boxes with the spherical nucleus located in the center of each cell. c. Columnar=are taller than they are wide; resemble rectangles with the elongated nuclei tend to crowd into a narrow band close to the basal lamina. E. Diversity of Epithelial Tissues 1. Simple squamous epithelium a. Description: single layer of flattened cells with a disc-shaped central nuclei and sparse cytoplasm. b. Function: allows passage of materials by diffusion and filtration in sites where protection is not important. Also secretes lubricant. c. Locations: Kidney glomeruli, air sacs of lungs, capillaries, linings of heart and lymphatic system. 2. Stratified squamous epithelium a. Description: thick layers of flattened cells; often keratinized layer and a mitotic layer. b. Function: protects underlying tissues in areas subject to abrasion c. Location: non-keratinized type lines the mouth and vagina; keratinized type forms the epidermis of skin. 3. Simple cuboidal epithelium a. Description: single layer of cube-like cells with large spherical centrally located nuclei. b. Function: secretion and absorption c. Locations: Kidney tubules, ducts and secretory portions of glands, ovary surface 4. Stratified cuboidal epithelium a. Relatively rare in the human body. b. Most common along the ducts of sweat glands, mammary glands, and other exocrine glands. c. DO NOT NEED TO KNOW FOR THE LAB PRACTICAL!! 5. Simple columnar epithelium a. Description: single layer of tall cells with round to oval nuclei; some cells bear cilia; may contain goblet cells that produce mucus; may contain microvilli. b. Function: absorption; secretion of mucus and enzymes; cilia propel substances. c. Location: non-ciliated type lines digestive tract, gallbladder, and ducts from glands; ciliated type lines small bronchi, uterine tubes, and uterus. 6. Stratified columnar epithelium a. Relatively rare in the human body. b. Most often found lining large ducts such as those of the salivary glands and pancreas. c. DO NOT NEED TO KNOW FOR THE LAB PRACTICAL!! 7. Pseudostratified columnar epithelium a. Description: single layer of cells of differing heights so that nuclei are a differing levels; may contain goblet cells and bear cilia. b. Function: secretion, propulsion by ciliary action. c. Location: non-ciliated type lines male reproductive ducts; ciliated type lines much of respiratory tract. 8. Transitional epithelium a. Description: resembles both stratified squamous and stratified cuboidal. Basal cells are cuboidal or columnar; surface cells are dome shaped. b. Function: stretches readily and permits distension. c. Location: Lines uterus, bladder, and urethra F. Glandular Epithelia are Specialized for Secretion 1. Endocrine glands= “ductless” glands that produce hormones. Secrete directly into interstitial fluids or bloodstream. Examples: pituitary gland, adrenal gland, thyroid gland, etc. 2. Exocrine glands=glands possessing ducts. Exocrine glands secret their substance either on the body surfaces or within ducts. They general demonstrates one of two different modes secretion: a. Merocrine=secrete products from secretory vesicles by exocytosis. Most common type. Example: salivary glands of the oral cavity b. Holocrine=accumulate products until the cell ruptures. Destroys the cell and must be replaced by cell division. Example: sebaceous glands of the skin c. Apocrine=products accumulate within the cells then the apex of the cell pinches off packets that contain the secretion. Example: mammary gland of the breast 3. Exocrine glands are unicellular or multicellular. a. Unicellular=goblet cells that produce mucin which mixes with water to form mucus. b. Multicellular=two structural classes: i. Simple=a single duct that does not branch on its way to the secretory cells (examples: gastric glands, sebaceous glands) ii. Compound= duct divides one or more times on its way to the secretory cells (examples: duodenal glands, mammary glands and salivary glands) Connective Tissues: Supports and Protects A. Location of Connective Tissues 1. Most abundant tissue in the body. 2. Never exposed to the outside environment. B. Characteristics of Connective Tissues 1. All types of connective tissue originate from mesenchyme. 2. Connective tissues vary widely in appearance and function but all forms share three basic components: a. Specialized cells=the cells present in each type of connective tissue helps to distinguish the various types from one another. A few of the cells are listed here: i. Fibroblast cells=produce connective tissue proper ii. Chondrocytes=produce cartilage iii. Osteocytes=produce bone iv. Hemocytoblast cells=produce blood b. Extracellular proteins fibers=three primary fibers are produced in connective tissues i. Elastic fibers=slender, straight, and very stretchy. They recoil to their original length after stretching or distortion. ii. Collagen fibers=thick, straight or wavy, and often forms bundles. They are very strong and resist stretching. iii. Reticular fibers=strong fibers that form a branching network or scaffolding c. Ground substance=material that fills the space between cells and surrounds the extracellular fibers. In some connective tissues the ground substance is gel-like while in others it is liquid based and in others it is rigid or calcified. Ground substance and extracellular fibers make up the matrix of connective tissues. 3. Many types of connective tissue are highly vascular and contain sensory receptors that detect pain, pressure, temperature, and other stimuli. C. Functions of Connective Tissues 1. Establish a structural framework for the body. 2. Transport fluids and dissolved materials. 3. Protect delicate organs. 4. Support, surround, and interconnect other types of tissue. 5. Store energy reserves, especially in the form of triglycerides. 6. Defend the body from invading microorganisms. D. Diversity of Connective Tissues 1. Connective Tissue Proper=includes connective tissues with many types of cells and extracellular fibers in a gel-like ground substance. a. Loose Connective Tissues – fibers created a loose, open framework i. Areolar tissue=most common form of connective tissue proper in adults. It is the general packing material in the body. Attaches skin to underlying body parts and is sometimes called the superficial fascia. All of the cell types found in other forms of connective tissue proper can be found in areolar. ii. Adipose tissue=found deep to the skin, especially at the flanks, buttocks, and breasts. It also forms a layer that provides padding within the orbit of the eyes, in the abdominopelvic cavity, and around the kidneys. The distinction between areolar tissue and adipose is the larger number of adipocytes (fat cells). iii. Reticular tissue=found in the liver, kidney, spleen, lymph nodes, and bone marrow, where it forms a tough, flexible network that provides support and resists distortion. In reticular tissue, reticular fibers create a complex supporting network known as a stroma. Fixed macrophages and fibroblasts are present but these cells are seldom visible. DO NOT NEED TO KNOW FOR THE LAB PRACTICAL!! b. Dense Connective Tissues – fibers are densely packed together i. Dense regular=all collagen fibers are oriented parallel to each other providing strength along the axis of the collagen fibers. Found in cords (such as tendons) or sheets (ligaments). Tendons connect muscle to bones. Ligaments connect bones to bones. ii. Dense irregular=collagen fibers are non-parallel forming an interwoven network. These tissues provide strength in many directions and are particularly important in areas subjected to stress from many directions such as the dermis of the skin. iii. Elastic=when elastic fibers outnumber collagen fibers, the tissue has a springy, resilient nature that allows it to tolerate cycles of extension and recoil. This elastic tissue is bound between the vertebrae of the spinal column and the erectile tissues of the penis. DO NOT NEED TO KNOW FOR THE LAB PRACTICAL!! 2. Fluid Connective Tissues=have distinctive populations of cells suspended in a watery matrix that contains dissolved proteins. NOT ON LAB PRACTICAL! a. Blood – flows within the cardiovascular system 3. Supporting Connective Tissues=differ from connective tissue proper in have a less diverse cell population and a matrix containing much more densely packed fibers. Supporting connective tissues protect soft tissues and support the weight of part or all of the body. a. Cartilage – solid, rubbery matrix containing chondrocytes. All cartilage is surrounded by a membrane of connective tissue called the perichondrium. i. Hyaline cartilage=found connecting the ribs to the sternum, covering the articular surfaces of long bones, supporting the respiratory passageways such as the trachea, and forming the tip of the nose and part of the nasal septum. Has an amorphous matrix with few visible fibers. It provides stiff but somewhat flexible support and reduces friction between bony surfaces. ii. Elastic cartilage=found in the ear and epiglottis. Has many more elastic fibers within the matrix and is therefore more flexible. iii. Fibrous cartilage=found within the intervertebral discs, the meniscus of the knee, and pubic symphysis. Has many more collagen fibers within its matrix and is therefore very strong. b. Bone – solid, crystalline matrix containing osteocytes. All bone is surrounded by a membrane of connective tissue called the periosteum. NOT ON LAB PRACTICAL! c. Comparison of cartilage and bone. Muscle Tissue in Motion (discussed in detail in Chapter 10-11) NOT ON LAB PRACTICAL! A. Highly vascularized muscular tissue is comprised of elongated cells (called fibers) containing myofilaments (actin and myosin proteins). 
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