Pathophysiology Module Outline PDF

PATHOPHYSIOLOGY MODULE OUTLINE among the most common causes of cell injury. I. Introduction to Pathophysiology II. Causes of Cell Injury III. Adaptation to Cell Injury IV. Ce...

PATHOPHYSIOLOGY MODULE OUTLINE among the most common causes of cell injury. I. Introduction to Pathophysiology II. Causes of Cell Injury III. Adaptation to Cell Injury IV. Cell Death The most common cause of hypoxia V. Inflammation is ischemia resulting from an arterial VI. Tissue Repair obstruction, but oxygen deficiency VII. The Immune System at a Glance also can result from inadequate oxygenation of the blood, as in a variety of diseases affecting the I. Introduction to Pathophysiology lung, or from reduction in the oxygen-carrying capacity of the The field of pathophysiology is blood, as with anemia of any cause, devoted to understanding the causes of and carbon monoxide (CO) disease and the changes in cells, tissues, and poisoning. organs that are associated with disease and give rise to the presenting signs and 2. Toxins. symptoms in patients. These include air pollutants, Etiology - refers to the underlying insecticides, CO, asbestos, cigarette causes and modifying factors that are smoke, ethanol, and drugs. responsible for the initiation and Many drugs in therapeutic doses can progression of disease. cause cell or tissue injury in a susceptible patient or in many Pathogenesis - refers to the individuals if used excessively or mechanisms of development and inappropriately. progression of disease, which account for Even innocuous substances, such as the cellular and molecular changes that give glucose, salt, water and oxygen, can rise to the specific functional and structural be toxic. abnormalities that characterize any particular disease. 3. Infectious agents. *Thus, etiology refers to why a All types of disease-causing disease arises and pathogenesis describes pathogens, including viruses, how a disease develops. bacteria, fungi, and protozoans, injure cells. II. Causes of Cell Injury 4. Immunologic reactions. 1. Hypoxia and Ischemia. Examples are autoimmune reactions Hypoxia, which refers to oxygen against one’s own tissues, allergic deficiency, and ischemia, which reactions against environmental means reduced blood supply, are MODULE 1 – INTRODUCTION TO PATHOPHYSIOLOGY– Prepared by: Michael Angelo O. 1 Sumugat RMT, MD  PATHOPHYSIOLOGY substances, and excessive or chronic 7. Physical agents. immune responses to microbes. Trauma, extremes of temperature, In all of these situations, immune radiation, electric shock, and sudden responses elicit inflammatory changes in atmospheric pressure all reactions, which are often the cause have wide-ranging effects on cells. of damage to cells and tissues. 8. Aging. 5. Genetic abnormalities. Cellular senescence results in a Genetic aberrations can result in diminished ability of cells to respond pathologic changes as conspicuous to stress and, eventually, the death as the congenital malformations of cells and of the organism. associated with Down syndrome or as subtle as the single amino acid III. Adaptation to Cell Injury substitution in hemoglobin giving rise to sickle cell anemia. A. Overview of cellular adaptation As a consequence of deficiency of - Adaptation is the cell’s reaction to functional proteins, such as enzymes prolonged stress and repeated injury in inborn errors of metabolism, or to protect itself and prevent recurrent injuries accumulation of damaged DNA or - Adaptations are either physical misfolded proteins, both of which (morphologic) or functional trigger cell death when they are beyond repair. B. Etiologies of cellular adaptation 6. Nutritional imbalances. 1. Atrophy: A decrease in size or numb er of cells; atrophy is due to a Protein–calorie insufficiency among decline in blood flow, nerve or impoverished populations remains a hormone supply, or nutrition major cause of cell injury, and 2. Hypertrophy: An increase in cell size specific vitamin deficiencies are not ; It is due to increased workload uncommon even in developed (exercise) or increased hormone countries with high standards of supply living 3. Hyperplasia: An increase in the num Ironically, excessive dietary intake ber of cells; hyperplasia is due to may result in obesity and also is an chronic irritation or increased important underlying factor in many stimulation (increased hormone diseases, such as type 2 diabetes levels or clinical abnormalities) mellitus and atherosclerosis. 4. Metaplasia: A change from one mat ure cell type to a different mature ce ll type; metaplasia is a benign MODULE 1 – INTRODUCTION TO PATHOPHYSIOLOGY– Prepared by: Michael Angelo O. 2 Sumugat RMT, MD  PATHOPHYSIOLOGY process and is usually reversible a. Forms (e.g., metaplasia from squamous epithelium to glandular epithelium) 1. Coagulation necrosis: Usually due to 5. Dysplasia: A change from a mature hypoxia, when cell type to an immature cell type - denaturation occurs and the cells abnormal cell differentiation); maintain their architecture for a few - dysplasia is partially reversible and is days (e.g., myocardial infarction) considered premalignant; it can have many etiologies (e.g., viruses, 2. Liquefactive necrosis: Results in the smoking, chronic exposure, transformation of cells into thick liqu persistent metaplasia, hyperplasia); id and complete loss of their morphologically, dysplasia results in structure (e.g., bacterial infection) abnormal cellular and nuclear features 3. Caseous necrosis: Cells become amo rphous and lose their architecture (e IV. Cell Death.g., granulomatous inflammation in tuberculosis or fungal infection) 1. Reversible Cell Injury - Swelling of cell organelles 4. Fat necrosis: Enzymatic necrosis that (endoplasmic reticulum, is seen in fat mitochondria) and swelling of the tissue (e.g., fat necrosis in the breast entire cell or pancreas) - Nuclear changes such as hyperchromasia (clumping of 5. Fibrinoid necrosis: Deposition of fibr nuclear chromatin) in in the blood - Other changes include cytoplasmic vessels (e.g., autoimmune disease) densities, membrane blebbing, and detachment of ribosomes Apoptosis 2. Irreversible Cell Injury - The programmed death of individual - Injury that leads to cell death by cells (not groups necrosis of cells) - Injury that leads to cell death by - Site: Normal tissue (e.g., endometriu apoptosis m, fetal tissue) or abnormal tissue (e.g., tumor cells) Necrosis - Initiation: The activation of caspases - The death of groups of cells due to , which is injury (always pathologic and never monitored by several genes (e.g., TB occurs in normal tissue), which 53 suppressor gene [apoptosis gene] results in the release of multiple and BCL-2 [antiapoptotic gene]) cellular components that will trigger an inflammatory reaction MODULE 1 – INTRODUCTION TO PATHOPHYSIOLOGY– Prepared by: Michael Angelo O. 3 Sumugat RMT, MD  PATHOPHYSIOLOGY Main morphologic characteristics of - The goal of acute inflammation is to apoptosis that differentiate it from limit injury and restore tissue necrosis: - The outcome of acute inflammation The cells and cellular organelles can be complete resolution, shrink abscess formation, regeneration, The cell membrane remains intact scar formation, or chronic Chromatin becomes condensed inflammation Cytoplasmic buds and apoptotic - Neutrophils are the main cells in bodies form acute inflammation V. Inflammation 2. Chronic inflammation - Is prolonged, active inflammation (la - Refers to both a protective response sting weeks to years) associated intended to eliminate the initial with tissue destruction and repair cause of cell injury and the necrotic cells and tissues resulting from the - Chronic inflammation is usually original insult. preceded by acute inflammation - Inflammation can be acute or chronic (e.g., bacterial infections, viral infections), although there are 1. Acute Inflammation exceptions (e.g., chronic - An early response to injury (within h granulomatous inflammation ours to days) [tuberculosis, sarcoidosis], that initiates vascular changes autoimmune diseases) (dilatation, increased permeability of the fluid), cellular changes, and - Consists of several phases, including leukocyte (white blood cell) necrosis, parenchymal damage, accumulation granulation tissue formation, and fibrosis (scar formation) - The leukocyte response to injury starts the inflammation process - Lymphocytes are the main cells in when leukocytes exit the blood chronic inflammation, but vessels through margination, rolling, macrophages, plasma cells, adhesion, and transmigration and monocytes, and eosinophils also start chemotaxis play a role - The vascular and cellular changes VI. Tissue Repair lead to the classic clinical signs and - This process follows acute and symptoms of acute inflammation chronic inflammation with the (redness, heat, swelling, pain, and intention to restore the normal limited function) tissue structure; it requires that some of the original cells are still MODULE 1 – INTRODUCTION TO PATHOPHYSIOLOGY– Prepared by: Michael Angelo O. 4 Sumugat RMT, MD  PATHOPHYSIOLOGY immune cells inhabit lymphoid viable; the ability of these cells to tissues & circulate in body fluids. replicate (regenerate) depends on the cell type as follows: - Functions to protect the body from: 1. Labile cells (e.g., stem cells, hemato A. Most infectious microorganisms poietic cells) replicate throughout B. Cancer cells their lives to replace lost cells C. Transplanted organs 2. Stable cells (e.g., fibroblasts) can D. Grafts replicate only when activated to E. Any other foreign materials replace lost cells 3. Permanent cells (e.g., cardiac and s - Can act directly – by cell attack triated muscle cell) cannot replicate - Can act indirectly – by releasing mobilizing scar tissue (fibrosis) and lost cells chemicals & antibody molecules. will be replaced by scar tissue Terminology: - Granulation tissue is the main type of tissue in the process of tissue 1. Pathogen: microorganism that is repair, consisting of new blood able to cause disease vessels, fibroblasts, and collagen; 2. Pathogenicity: the ability of a tissue repair and the formation of microorganism to cause disease. collagen are stimulated and 3. Virulence: the degree of monitored by special genes pathogenicity. and chemical mediators such as 4. Opportunistic pathogens: bacteria platelet-derived blood factor (PDGF), which cause disease in a tissue growth factor beta (TFG-b), compromised host. fibroblastic growth factor (FGF), and 5. Normal flora: harmless bacteria vascular endothelial growth factor consistently associated with the (VEGF) host. 6. Infection: when an organism (incl. Normal flora) breaches a body The Immune System – At A Glance surface. The Immune System: - Doesn’t necessarily lead to disease - The immune system is more a functional ▪ Depends on: system rather than an anatomical or organ-based system. Route of entry Number of pathogens Consists of: Immune status of host - a diverse array of molecules - trillions of immune cells (especially lymphocytes). These molecules & MODULE 1 – INTRODUCTION TO PATHOPHYSIOLOGY– Prepared by: Michael Angelo O. 5 Sumugat RMT, MD  PATHOPHYSIOLOGY Defense Systems of the Body: both the target and themselves. (kamikaze) I. Innate (non-specific) Immune System: - “the body’s foot-soldiers” Eosinophils – another type of - Already in place at birth. white blood cell – kill - Is always prepared parasitic worms. - Responds within minutes Basophils – important in - Protects the body from all foreign allergic reactions substances. 3. Fever - Are often sufficient to ward off invading - When exposed to foreigners, pathogens single-handedly. leukocytes & macrophages secrete - Essentially, it reduces the workload of the pyrogens > increases the body’s adaptive system. thermostat. - Increases metabolic rate, kills microbes, speeds up repair. 1ST Line of Defense: Surface Barriers: 4. Natural Killer cells ▪ Prevents Entry of Pathogen - Police the body in blood & lymph 1. Skin - Can lyse & kill cancer cells & o Stratified virus-infected cells o Heavily keratinized - Target all cells that lack ‘self’ 2. Mucous membranes surface receptors (non-specific) o o Lysozyme: enzyme found in saliva Kill by latching onto invaders and & tears >destroy bacteria. inducing apoptosis. o Sticky Mucus: in digestive & - Also secrete potent chemicals respiratory tract > traps bacteria. that promote inflammation o Cilia – nasal &respiratory>sweep 5. Antimicrobial proteins bacteria into mouth > swallowed. - Either attack microbes directly or o Acid secretion: skin, vagina, reduce their reproductive ability; stomach > kills microbes. Interferons’ & ‘compliment’ 6. Inflammation 2ND Line of Defense: Internal Defenses: - In response to physical ▪ Prevents Spread of Pathogen If Surface trauma/intense heat/bad Barriers are Breached chemicals/infection. 1. Phagocytes - Prevents spread of damaging agents Macrophages – Large to nearby tissue phagocytic cells - Disposes of cell debris & 2. Granulocytes – possess cytoplasmic pathogens granules - Sets stage for repair. Neutrophils –they release - Characterized by heat, redness, toxic chemicals into the pain & swelling extracellular fluid, killing MODULE 1 – INTRODUCTION TO PATHOPHYSIOLOGY– Prepared by: Michael Angelo O. 6 Sumugat RMT, MD  PATHOPHYSIOLOGY - Antigen causes activation of II. Adaptive (specific)Immune System: macrophages, NK-cells, T-lymphocytes & cytokines - “The body’s elite special forces” – equipped with high-tech weapons. Macrophages & NK-Cells – destroy - Adaptive responses are called into action intracellular pathogens as ‘reinforcements’ T Cells – induce apoptosis of body cells with - Takes much more time to mobilize than viruses/intracellular bacteria/cancerous the innate response. traits. - Attack specific foreign substances – incl. Cytokines are secreted – enhance Antigens and abnormal body cells inflammatory response and/or activate - When disabled > cancer, AIDS, etc. other lymphocytes/macrophages. Activated - Tremendously amplifies the inflammatory cells destroy infected/foreign cells. response. - >It is Specific: recognizes particular *******END OF MODULE 1********* pathogens/antigens - >It is Systemic: immunity isn’t restricted to initial infection site - >It has Memory: mounts stronger attacks on previously encountered pathogens. The body’s 3rd line of defense 1. Humoral Immunity (aka. Antibody- mediated immunity) -Immunity can be transferred from person- person via serum B cells (B Lymphocyte) - Make antibodies against soluble antigens. Antibodies (Immunoglobulins): - Circulate freely in blood & lymph - Neutralizes bacteria/toxins/& viruses > marks for destruction by phagocytes or compliment. 2. Cellular Immunity -Immunity can be transferred from person- person via blood cells MODULE 1 – INTRODUCTION TO PATHOPHYSIOLOGY– Prepared by: Michael Angelo O. 7 Sumugat RMT, MD  Pathophysiology INVESTIGATIONS MODULE 2 OUTLINE skin scrapings, hair, and nail clippings analyzed with potassium I. Common Skin Infections hydroxide (KOH) prep (since these fungi live a. Dermatophytosis as molds, look for hyphae, and mycelia) i. Tinea Capitis ii. Tinea Corporis MANAGEMENT iii. Tinea Cruris topicals may be used as first line iv. Tinea Pedis agents for tinea corporis/cruris and tinea v. Tine Manuum pedis (interdigital type), e.g. clotrimazole or vi. Tine Unguium terbinafine cream applied bid, continued till b. Candidiaisis one week after complete resolution of i. Cutaneous lesions ii. Oral iii. Pityriasis Versicolor oral therapy is indicated for c. Ectoparasitic onychomycosis, tinea capitus, e.g. i. Scabies terbinafine (Lamisil) or itraconazole ii. Pediculosis (Sporanox) d. Viral i. Warts itraconazole is a P-450 inhibitor. It ii. Herpes Simplex alters metabolism of non-sedating iii. Chicken Pox antihistamines, cisapride, digoxin, and HMG e. Bacterial CoA reductase inhibitors i. Impetigo ii. Furunculosis and Folliculitis A. Tinea Capitis iii. Abscess iv. Cellulitis DEFINITION v. Necrotizing Fasciitis non-scarring alopecia with scale vi. Gas Gangrene II. Skin Manifestation of Metabolic ETIOLOGY Diseases Trichophyton tonsurans and a. Jaundice Microsporum species III. Inflammatory Skin Disorders a. Psoriasis EPIDEMIOLOGY b. Urticaria affects children (mainly black), immunocompromised adults I. DERMATOPHYTOSIS very contagious and may be transmitted from barber, hats, theatre DEFINITION seats, pets infection of skin, hair and nails caused by a species of dermatophyte (fungi SIGNS AND SYMPTOMS that live within the epidermal keratin and round, scaly patches of alopecia do not penetrate deeper structures) may see broken off hairs if tissue reaction is acute, a Kerion ETIOLOGY (boggy, elevated, purulent inflamed Trichophyton, Microsporum, nodule/plaque) may form - this may be Pityrosporum, Epidermophyton species secondarily infected by bacteria and result in scarring PATHOPHYSIOLOGY digestion of keratin by EXAMINATION dermatophytes results in scaly skin, broken Wood’s light examination of hair: hairs, crumbling nails green fluorescence only for microsporum infection [MODULE 2 – DISORDERS OF THE SKIN] – Prepared by: Michael Angelo O. Sumugat, RMT MD  Pathophysiology culture of scales/hair shaft may be ETIOLOGY done on Sabourad’s agar T. rubrum, T. mentagrophytes, E. microscopic examination of a KOH floccosum preparation of scales or infected hair shafts reveal characteristic hyphae EPIDEMIOLOGY most common in adult males MANAGEMENT griseofulvin 15-20 mg/kg/day x 8 EXAMINATIONS weeks or terbinafine (Lamisil) 250 mg od x same as for Tinea corporis 2-4 weeks (vary dose by weight) DIFFERENTIAL DIAGNOSIS candidiasis (involvement of scrotum and DIFFERENTIAL DIAGNOSIS has satellite lesions) psoriasis, seborrheic dermatitis, alopecia erythrasma (coral-red fluorescence with areata, trichotillomania Wood’s lamp) contact dermatitis B. Tinea Corporis (Ringworm) D. Tinea Pedis (Athlete’s Foot) DEFINTION AND CLINICAL FEATURE pruritic, scaly, round/oval plaque with DEFINITION erythematous margin and central clearing pruritic scaling and/or maceration of the single or multiple lesions webspaces and powdery scaling of soles peripheral enlargement of lesions site: trunk, limbs, face CLINICAL FEATURES white vesicles, bullae, scale maceration ETIOLOGY interdigital T. rubrum, E. floccosum, M. cannis, T. cruris ETIOLOGY T. rubrum, T. mentagrophytes, E. EPIDEMIOLOGY floccosum most common in farm children and those with infected pets EPIDEMIOLOGY chronic infections are common in atopics EXAMINATIONS heat, humidity, occlusive footwear are microscopic examinations of KOH prep of predisposing factors scales scraped from active margin shows hyphae SIGNS AND SYMPTOMS scales may be cultured on sabourad’s agar Acute infection - red/white scales, vesicles, bullae, often with maceration DIFFERENTIAL DIAGNOSIS may present as flare-up of chronic tinea psoriasis pedis seborrheic dermatitis frequently become secondarily infected nummular dermatitis by bacteria pityriasis rosea Chronic - non-pruritic, pink, scaling C. Tinea Cruris (“Jock Itch”) keratosis on soles, and sides of foot, often in a “moccasin” distribution DEFINITION AND CLINICAL FEATURES sites: interdigital, especially in 4th scaly patch/plaque with a well-defined, webspace curved border and central clearing on medial thigh does not involve scrotum pruritic, erythematous, dry/macerated [MODULE 2 – DISORDERS OF THE SKIN] – Prepared by: Michael Angelo O. Sumugat, RMT MD  Pathophysiology MANAGEMENT EXAMINATIONS terbinafine (Lamisil) 250 mg od (6 weeks microscopic examination of a KOH prep of for fingernails, 12 weeks for toenails) or scales from roof of a vesicle or powdery pulse itraconazole (Sporanox) at 200mg bid scaling area x 7d, then 3 weeks off (2 pulses for culture of scales on sabourad’s agar fingernails, 3 pulses for toenails) DIFFERENTIAL DIAGNOSIS DIFFERENTIAL DIAGNOSIS dyshidrotic dermatitis psoriasis (pitting, may have psoriasis allergic contact dermatitis (dorsum/heel) elsewhere) atopic dermatitis trauma erythrasma, intertrigo (interdigital) lichen planus psoriasis (soles or interdigital) I.II CANDIDIASIS E. Tinea Manuum A. Cutaneous Candidiasis – (Candida CLINICAL FEATURES Albicans) acute: blisters at edge of red areas on Overgrowth of Normal Commensal of the hands mouth, vagina, or lower GIT.) chronic: single dry scaly patch - Only infects the outer layers of the primary fungal infection of the hand is epithelium of mucous membrane or actually quite rare; usually associated with skin. tinea pedis with one hand and two feet affected = “1 hand 2 feet” syndrome Presentation: Red, macerated area ETIOLOGY Glistening Surface same as in tinea pedis Scaling along the advancing border. The initial lesion is a papule that DIFFERENTIAL DIAGNOSIS then becomes a pustule. contact dermatitis, atopic dermatitis, Important clinical feature is the psoriasis (all three commonly mistaken for presence of ‘satellite’ pustules fungal infections) beyond the border of the main granuloma annulare (annular) infection. F. Tinea Unguium (Onychomycosis) Treatment: Topical Therapy DEFINITION AND CLINICAL FEATURES crumbling, distally dystrophic nails; B. Oral Candidiasis – (Candida yellowish, opaque with subungual Albicans) herperkeratotic debris toenail infections usually precede Presents as: fingernail infections White Patches easily scraped off to leave a red, raw base. ETIOLOGY Chronic red, raw gums, tongue and T. rubrum (90% of all toenail infections) buccal mucosa. EXAMINATION Treatment: Topical or Systemic Therapy KOH prep of scales from subungual scraping shows hyphae on microscopic C. Pityriasis versicolor – (Candida exam Albicans subungual scraping may be cultured on - Caused by normal Commensals ʹ Eg. Sabourad’s agar yeasts (Candida). - Common Superficial Fungal-Induced Rash [MODULE 2 – DISORDERS OF THE SKIN] – Prepared by: Michael Angelo O. Sumugat, RMT MD  Pathophysiology Presentation: Diagnosis: flaky, discolored patches on chest & Clinical Diagnosis: back. Chronic itch with Symmetrical Rash Small, well defined, slightly scaly Burrows patches Either Hyperpigmented or Skin Scraping - Look for Scabies Mites: Hypopigmented Intact larvae, nymphs or adults Unhatched or hatched eggs I. ECTOPARASITIC Molted skins of mites Fragments of molted skins A. Scabies Mite feces Organism: Treatment: - Sarcoptes scabiei (Scabies Mite) - Topical Permethrin or Oral Ivermectin Epidemiology: Environmental Measures: - Human infestations originating from Mites can contaminate bedding, pigs, horses and dogs are mild and chairs, floors, and even walls self-limiting. (Usually only a problem with crusted - Scabies infestations from other scabies) humans never cure without Wash, sun, vacuum, surface intervention. insecticide Community Prevention: Ecology: Treat all close contacts – Esp. in - Mites live in stratum corneum (Don’t Indigenous Communities get any deeperͿ Simultaneous Effective Treatment - Eat stratum corneal Keratinocytes - Make “tunnels” by eating TREAT AGAIN IN 7 DAYS - Mating occurs on the hosts skin - Fertilized Female Mites Burrow into B. Pediculosis - Head Lice the Stratum Corneum (1 mm deep) - Salivary Secretions contain 3 Types: Proteolytic Enzymes > Digest 1. Head Lice: Pediculus Humanus Capitis Keratinocytes. Epidemiology: - Common in Primary School Children Transmission: in the Tropics - High prevalence in children (50%) - Higher prevalence in Aboriginal and adults (25%) in tropical remote Children communities - Spread by close physical contact Diagnosis: - Conditioner + Fine-Tooth Come Presentation: - Wipe combings on white tissue - Itch (Exacerbated at night and after paper hot showers). - Itchy, Excoriated Rash on Trunk, 2. Body Lice: Pediculus Humanus Corporis associated with Scaly Burrows on - Live on clothes, and come to the body to the fingers and wrists. feed. - Often vesicles and pustules on the palms and soles and sometimes on 3. Pubic Lice: Phthirus Pubis the scalp. - Largely sexually transmitted - Blood Feeder [MODULE 2 – DISORDERS OF THE SKIN] – Prepared by: Michael Angelo O. Sumugat, RMT MD  Pathophysiology - Can infect any Body Hair - HPV 6 & 11 = Genital & Cutaneous (Pubic/Trunk/Legs/Axilla/Beard) but Warts rarely head. - HPV 16 & 18 = Cervical & Penile Ca Lifecycle: Appearance: Eggs laid in hair (knits) - Verrucous surface Larvae grow into adults - Can often see a tiny black dot in the Adults – blood sucking (live in hair) middle due to thrombosed capillary blood vessels Transmission: - head-head contact. Presentation: Presentation: - Common on back of fingers, toes - Scalp and Neck can be Itchy and knees - Nits are noticeable on the hairs. - Common Warts Diagnosis: (Skin/Plantar/Palmar) - Best Method = ͚Conditioner + Comb - Genital Warts (Cervix, Vulva, Penis) Technique͛: - NB: Cervical Papillomas - Can cause o Very Practical for parents cervical cancer. o Cost Effective - Laryngeal Papilloma o High Sensitivity o Conditioner ‘Stuns’ the lice No Reliable Treatment: by suffocating them - 50% of childhood warts disappear o Prevents them from running within 6mths; 90% are gone in 2 away years. - Many don’t bother with treatment. Management/Treatment: - Surgical Excision/Chemical Conditioner & Nit Comb Treatment/Cryotherapy/Electrosurg Physical Removal ery (Cauterize) Cut Hair Topical Insecticidal Cream Clinical Significance Good idea to wash pillows and hats - Contagious though – Hot Wash - Central blood vessels > Bleed (Treat all body hair – for Pubic lice) profusely when the surface is broken. Reasons for Treatment Failure: Inadequate application of the B. Herpes Simplex (Cold Sores/Genital product Lesions) Lice are resistant to insecticide Failure to retreat to kill nymphs What is it? emerged from eggs - Common Mucosal Viral Infection Reinfection. that presents with localized blistering II. VIRAL - Can reside in a latent state A. Viral Warts 2 Types: - Benign Tumors of the skin a. Type 1 - Common in children - Typically facial/oral infections (Cold - Infectious ʹ (Spread by direct sores/fever blisters) contact) - Occur mainly in infants & young kids Organism: b. Type 2 - Typically from HPV (human - Mainly Genital papilloma viruses) - Occur after puberty (often transmitted sexually) [MODULE 2 – DISORDERS OF THE SKIN] – Prepared by: Michael Angelo O. Sumugat, RMT MD  Pathophysiology Pathophysiology: Presentation: - Incubation Period = 2 weeks Stages of Infection: - (Chicken Pox) Initial Mucosal 1. Prodromal Stage Vesicle or "blister" Infection > Viraemia > Epidermal stage Lesions 2. Ulcer stage - May lead to Latent infection of 3. Crust stage Dorsal Ganglion Cells of Sensory Nerves. - The virus grows down the nerves - (Shingles) Reactivation of latent and out into the skin > Localized Varicella Zoster Virus in Peripheral Blistering Nerves - Neuralgia - Lymphadenopathy Signs/symptoms: - High Fever - Itchy rash or red papules - Recurrences can be triggered by: - Begins on the Trunk > Face and Minor trauma/Other Extremities infections/UV - May cover entire body radiation/Hormonal - High fever/headache/cold-like factors/Emotional symptoms/vomiting/diarrhea. stress/Operations/procedures on Diagnosis: face - Clinical Diagnosis - Immunofluorescence Treatment: - Test for Elevated VZV-Specific - Mild cases require no treatment Antibodies (IgM - Primary Infection; - Sun protection to prevent IgG - Second Infection) - Oral Antiviral Drugs (Stop the virus multiplying) Treatment: - Symptomatic Complications: - Resolves on its own. - Encephalopathy - Trigeminal Neuralgia (Neurogenic Complications: Pain) - Varicella During Pregnancy can cause Congenital Varicella C. Chicken pox (Herpes Varicella Syndrome: Zoster) o Spontaneous Abortion (3-8% in 1st Trimester) or IUGR What is it? - Skin: Cutaneous Defects, - Highly contagious disease Hypopigmentation - Typically childhood disease (before - Neuro: Intrauterine Encephalitis, 10yrs) Brain Damage, Seizures, - One infection thought to confer Developmental Delay lifelong immunity - Eye: Chorioretinitis, Cataracts, Anisocoria Organism: - MSK: Limb Hypoplasia - Varicella zoster virus (HHV3) (AKA: - Systemic: cerebral cortical atrophy Chicken Pox Virus, Varicella, Zoster) - Renal: Hydronephrosis, Hydroureter - GI: GORD Transmission: - CVS: Congenital Heart Defects - Highly Infectious - Perinatal Varicella Infection: - From person to person o severe mortality rate of 30% - Aerosol Droplets - Direct contact with fluid from open sore. [MODULE 2 – DISORDERS OF THE SKIN] – Prepared by: Michael Angelo O. Sumugat, RMT MD  Pathophysiology IV. BACTERIAL B. Folliculitis & Furunculosis (Boils): A. Impetigo (AKA School Sores) What is it? Folliculitis: What is it? - Acute pustular infection of a hair - Superficial Bacterial Skin Infection follicle - Most Common in school kids - Commonly after Waxing/Shaving - Very Contagious ʹ (Spread by Close Boils (Furuncles): Contact & Poor Hygiene) - A deep form of folliculitis. - Usually resolves slowly Organism: - Staphylococcus Aureus Organism: Presentation: - Mostly Staphylococcus Aureus - Folliculitis: An Erythematous Pustule - Sometimes Streptococcus Pyogenes centered on a Hair Follicle. - Can lead to Glomerulonephritis or - Boils (Furuncles): Tender, red Rheumatic Fever if it is Strep nodule which enlarges & may later discharge pus a. Staph. Aureus (Bullous) Treatment: b. Streptococcus (Non-bullous) - Treated aggressively with antibiotics and drainage. Presentations: - Occur most commonly on face C. Abscesses: - Fragile vesicles rupture & crust - Usually Staphylococcus Aureus - Can be confused with HSV - Begin as superficial infections of hair follicles (folliculitis) 1. Nonbullous/Crusted Impetigo: Organisms travel down Hair Follicles - (Most common) following Disruption (Eg. After - Yellow crusts and erosions Shaving) - Itchy/Irritating (but not painful). Development of boils (furuncles) 2. Bullous impetigo: - Number of boils cluster together = - Always due to S. Aureus carbuncle;͟ aka Abscess - Mildly irritating blisters that erode rapidly leaving a brown crust. D. Cellulitis: 3. Ulcerative lesions: What is it? - Always due to S. pyogenes. - Bacterial infection of the Dermis and - Most common in Aboriginal Sub-Cutaneous Tissues Communities Organism: Very Infectious - Adults: 90% due to Staph. - Epidemic in young children Aureus/GAS - Transmitted through skin contact - Children: H. influenzae b - Outbreaks associated with poor - Associated with cat/dog bite: hygiene / crowded living conditions Pasteurella multocida Treatment: Presentation: - Cover Affected Areas - Painful, raised and Edematous - Abstain from School Erythema. (Most commonly on - Systemic or Topical Antibiotics Lower Leg) - Possible Blistering - Lymphadenopathy - & Malaise & Fever. [MODULE 2 – DISORDERS OF THE SKIN] – Prepared by: Michael Angelo O. Sumugat, RMT MD  Pathophysiology - Toxins are produced > Cause the Tissue Death and associated Distribution: Symptoms - Children - Periorbital Area - Adults - Lower Legs Presentation: - Inflammation at the Site of Infection There’s usually an underlying cause: - Brownish-red and extremely painful - Lymphoedema tissue swelling - Tinea, Herpes simplex infection, - Gas may be felt in the tissue when - Chronic sinus infection the swollen area is pressed - Chronic dermatitis - Margins of the infected area expand - Poor lower leg circulation rapidly (Within a few minutes) - Wounds Prognosis: Treatment: - The involved tissue is completely - Antibiotics destroyed (Toxin-Mediated Destruction) E. Necrotizing Fasciitis: - Medical Emergency - Often needs G. Mycobacterial Infections: Radical Debridement of Necrotic Tissue 1. Leprosy: - Tuberculoid and lepromatous forms Organisms: - Mainly affect skin and nerves - Group A Strep (GAS) - Staph. Aureus SKIN MANIFESTATION OF METABOLIC - (Both cause severe, systemic DISEASES – JAUNDICE toxicity) - Others (Vibrio, Clostridium, BILIRUBIN Bacteroides)  Bilirubin is a yellow breakdown Pathogenesis: product of normal heme catabolism. - The Necrosis is Toxin-Mediated > YOU CAN’T JUST TREAT WITH  Its levels are elevated in certain ANTIBIOTICS diseases, and it is responsible for the - Not due to a Flesh Eating Bacteria yellow color of bruises and the brown color of feces. Types:  Bilirubin reduction in the gut leads to a product called urobilinogen, Type I - Polymicrobial Infection which is excreted in urine. Type II - Monomicrobial Infection  It is thought to be a toxin because it F. Gas Gangrene: is associated with neonatal jaundice, possibly leading to irreversible brain Organism: damage due to neurotoxicity. - Clostridium perfringens  Like these other pigments, bilirubin Pathogenesis: changes its conformation when - Generally, occurs at site of trauma exposed to light. This is used in the or recent surgical wound phototherapy of jaundiced - Usually only occurs with Poor Blood newborns: the illuminated version of Supply (E.g. Diabetes) bilirubin is more soluble than the - Anaerobic conditions unilluminated version. [MODULE 2 – DISORDERS OF THE SKIN] – Prepared by: Michael Angelo O. Sumugat, RMT MD  Pathophysiology - This yellow color is caused by a high BILIRUBIN FORMATION level of bilirubin, a yellow-orange bile pigment. Bile is fluid secreted by - Erythrocytes (red blood cells) the liver. generated in the bone marrow are destroyed in the spleen when they - Jaundice may be noticeable in the get old or damaged. sclera (white) of the eyes at levels of about 30-50 μmol/l, and in the skin - This releases hemoglobin, which is at higher levels. Jaundice is classified broken down to heme, as the globin depending upon whether the parts are turned into amino acids. bilirubin is free or conjugated to glucuronic acid into: - The heme is then turned into unconjugated bilirubin in the 1. Conjugated jaundice macrophages of the spleen. 2. Unconjugated jaundice - Bilirubin is bound to albumin and - Jaundice also can be classified into transported in plasma from the three categories, depending on reticuloendothelial system to the which part of the physiological liver, as unconjugated bilirubin. mechanism and the pathology affects. The three categories are: - In the liver, bilirubin is made water soluble by hepatocytes which 1. Pre-hepatic: The pathology is conjugate bilirubin with glucuronic occurring prior the liver acid to form conjugated bilirubin 2. Hepatic: The pathology is located (BC). within the liver 3. Post-Hepatic: The pathology is - BC is secreted from hepatocytes to located after the conjugation of the bile canaliculi of the liver and is bilirubin in the liver transported from the liver via the gall bladder and common bile duct Pre-hepatic jaundice is caused by anything to the gastrointestinal tract. which causes an increased rate of hemolysis (breakdown of red blood cells). As seen in: - In the ileum and colon, bacteria - Malaria convert bilirubin into - Certain genetic diseases, such as stercobilinogen. sickle cell anemia, spherocytosis and glucose 6-phosphate dehydrogenase - Stercobilinogen is oxidized to deficiency stercobilin, which is excreted in the - Commonly, diseases of the kidney. feces. Hepatic jaundice causes include: - While most bilirubin is excreted as - Acute Hepatitis stercobilin, a small amount of - alcoholic liver disease. stercobilinogen is reabsorbed into - Neonatal jaundice, is common, the blood, modified by the kidneys, occurring in almost every newborn and excreted as urobilinogen in the as hepatic machinery for the urine. conjugation and excretion of bilirubin does not fully mature until JAUNDICE approximately two weeks of age. - Jaundice is a condition in which the Post-hepatic jaundice, also called skin, sclera (whites of the eyes) and obstructive jaundice, is caused by an mucous membranes turn yellow. interruption to the drainage of bile in the biliary system. [MODULE 2 – DISORDERS OF THE SKIN] – Prepared by: Michael Angelo O. Sumugat, RMT MD  Pathophysiology - The most common causes are gallstones in the common bile duct, B. Urticaria (Hives): and pancreatic cancer in the head of the pancreas. Also, a group of Etiology parasites known as "liver flukes" live in the common bile duct, causing - Type I hypersensitivity – Allergy obstructive jaundice. (Food/drug/plant/etc) - The presence of pale stools and dark Pathogenesis: urine suggests an obstructive or post-hepatic cause as normal feces - Antigen is Re-Exposed to a sensitized get their color from bile pigments. Mast-Cell/Basophila IgE-Bound Mast Cell Degranulates: § àReleasing - Patients also can present with Inflammatory Mediators (Histamine) elevated serum cholesterol, and of Type-1-Hypersensitivity often complain of severe itching. Reactions. - Perivascular inflammatory infiltrate: lymphocytes, neutrophils or INFLAMMATORY SKIN DISORDERS eosinophils. A. Psoriasis Clinical Significance Etiology - Multifactorial (Genetic & Immune) - Usually on trunk and extremities. - Individual lesions are transient, Pathogenesis: usually resolve in 24 hr, but entire - Sensitized T cells infiltrate the skin episode may last for days. and secrete cytokines and growth - All ages, more in 20 – 40y. factors > Continuous stimulation of basal cellsa > Increased cell turnover > Inflammation, Vascular Proliferation Angiogenesis ********END OF MODULE 2******** Morphology Gross: - Plaque covered with Silvery Scales (Due to Hyperkeratosis & Parakeratosis) - Bilateral - Well-Demarcated - Erythematous Based Clinical Significance (List 3x Clinical Features): Can cause Multi-System Disorder: - Arthritis - Myopathy - Enteropathy - Immunodeficiency - Nail Pitting Auspitz Sign: - Micro bleeding when crusts are removed. [MODULE 2 – DISORDERS OF THE SKIN] – Prepared by: Michael Angelo O. Sumugat, RMT MD  Pathophysiology BONE INJURIES Neurovascular compromise – can pull / tear / compress Module Outline /rupture surrounding nerves/vessels. I. Bone Injuries a. Fracture and Dislocations Dislocations: II. Arthropathies - The Displacement of Joint Surfaces a. Crystal arthropathy such that Normal Articulation no i. Gouty arthritis longer occurs. b. Degenerative arthropathy - When forces on joint are greater i. Osteoarthritis than stabilizing forces of Bone, c. Seropositive/immunologic Ligament & Muscle. arthropathy - Emergency Because: i. Rheumatoid arthritis The longer the delay before d. Infectious arthritis reduction, the more difficult i. Septic arthritis it becomes, as the muscles III. Degenerative Bone disease around the joint contract. a. Osteoporosis Delay can also result in IV. Bone and Muscle infection significant joint & ligament a. Osteomyelitis damage > Impairment of function. Neurovascular compromise Key words + Definitions: – can pull / tear / compress /rupture surrounding 1. Fracture: A Break in a Bone nerves/vessels. 2. Compound fracture: An Open Dismemberment: Fracture where there is broken skin. - Loss of limb or Extreme Tissue-loss 3. Dislocation (or “Luxation”): The resulting in permanent functional Displacement of Joint Surfaces with impairment of that limb. Abnormal Articulation. 4. Reduction: Restoration of a fracture Factors Affecting the Degree of Urgency: or dislocation to the correct - Abnormal ABC alignment. - Bleeding 5. Splint: Medical device for - Major Vascular Compromise immobilizing limbs/spine to prevent - Open Vs. Closed Injury further injury - Neurological Compromise 6. Neurovascular compromise: Vessels - Pain /Nerves Damage due to injury > - Potential Loss of Function if Injury functional impairments. is Untreated. 7. Compartment syndrome: Bleeding/Swelling into a muscle The Basic Priorities of MSK Care: compartment > Compress - Primary Survey – “ABC” (Life before vessels/nerves. Limb) - Identify Injury What is a Musculoskeletal Emergency? - Analgesia - Splint Fractures: - Prevent Infection - Breaks in Bone. - Reduction (Restoring Alignment) - Emergency Because: If it’s an ‘Open Fracture’ – Benefits of Reduction & Splinting: Risk of Infection - Splinting: Some fractures won’t heal o Reduces Pain without treatment o Reduce Bleeding MODULE 3 – MUSCULOSKELETAL - Prepared by: Michael Angelo Sumugat RMT, MD 1  Pathophysiology o Promote Healing - Risk of NV-Compromise – can o Reduce risk of Further pull/tear/compress/rupture Compromise (Bone / Neuro / surrounding nerves/vessels. Vascular/ Functional) - Risk of Compartment Syndrome - Bleeding into muscle compartments - Reduction: > Compresses > blood vessels and o Reduce Pain nerves > ;May lead to “Crush o Restore Function Syndrome” o Reduce risk of Further Compromise(Neuro/Vascular NB: Crush Syndrome: Muscle /Functional) Ischemia/Necrosis due to Compartment Syndrome > pain, Swelling, Inflammation, FRACTURES & FRACTURE HEALING: DIC, Rhabdomyolysis > Limb Amputation. - Etiology: Treatment: o *Traumatic Injury o Reduction (Either Open or Closed o Pathological Fracture – (Osteolytic Reduction) Bone Metastasis, or Osteoporosis) o Immobilization (Splint / Cast / Rod /Pins/Brace/etc.) Mechanisms of Fracture Healing: o Analgesia o Rest > Physio 1. (1-3days) - Hematoma & Inflammation (Blood Clot + Fibrin Mesh) Morphology of Fractures (Refer to PPT) 2. (1-3weeks) - Soft Callus (Deposition of 1. Transverse Osteoid + Granulation Tissue + Fibroblasts) 2. Spiral 3. (1-2mths) - Hard Callus (Mineralization of 3. Oblique Osteoid)– NB: VISIBLE ON XRAY 4. Linear 4. (>2mths) - Remodeling of Woven Bone 5. Incomplete with Lamellar Bone 6. Impacted 7. Greenstick Bone Remodeling: 8. Comminuted - Bone remodels in response to: 9. Compound Calcium requirements in body...and ARTHRITIS Mechanical Stress Physical Activity (Stress) A. CRYSTAL ARTHROPATHIES - GOUTY Nutrition ARTHRITIS Vitamin D Age GOUT (GOUTY ARTHRITIS): Hormones (Eg. PTH, PHRP) Etiology: o Resorption – destruction of old bone - Anything that causes increased Urea matter by Osteoclasts Production or decreased Urea Excretion (Eg. High Protein/Alcohol o Apposition – deposition of new bone Diet) matter by Osteoblasts - (NB: Also Secondary Causes ʹ Eg. Renal Failure, Thiazides, Clinical Features: Hypothyroidism, Hemolysis, Obesity) Emergency Because: Pathogenesis: - Risk of Infection - If a - Derangement in Purine Metabolism ‘Compound/Open Fracture’. > Hyperuricemia > Monosodium - Some require treatment to heal. Urate Crystal Deposition in Joint tissue > Forms “Tophi”͟ > Chronic MODULE 3 – MUSCULOSKELETAL - Prepared by: Michael Angelo Sumugat RMT, MD 2  Pathophysiology Inflammation > Destruction of the Pathogenesis tissue - Mechanical, then Inflammatory: Cartilage Hydration Decreases Morphology: with Age > Less Resistant to Friction > Cartilage Erosion > Exposure of Bone > Macro: Red, Hot, Swollen Joints (Typically Grinding > Mechanical Damage & 1st MTP Joint & Hands) + Gouty Tophi Inflammation Clinical Features: Morphology: - Typically Males >45yrs 1. Eburnation of Bone (Shiny, thickened, hardened bone) Recurrent Severely Painful Episodes of 2. Cartilage Degeneration Acute Arthritis: 3. Peripheral Osteophytes > “Joint - Typically Lower Extremities First (1st Lipping” (New bone formation MTP Joint) around the joint edges) - Can also affect Hands - May mimic Cellulitis (But will have Clinical Features: decreased ROM͕; Cellulitis has - Typically in >40yrs normal ROM - Attacks last 1wk. Symptoms: - Large, Weight-Bearing Joints (Knees, Gouty Tophi:͟ Spine) - Urate deposition in Joints, - Nodular/Bulky, Painful Joints + Joint- Cartilage, Bursae, & Soft Tissues) Line Tenderness - Common Sites: 1st MTP joint, - Pain Worse with Activity & Cold Tendon Insertions, Pressure Points Weather - Painless͕ but decreased ROM - Pain Better with Rest. - Joint Instability & Crepitus (due to Effects on Kidney: irregular joint surface) > decreased - Uric Acid Stones ROM with Muscle Wasting - Urate Nephropathy - Bony Overgrowths (Osteophytes) > Nodules – (“Bouchard’s nodes” in Diagnosis: PIP Joints and “Hebeden Nodes” in - Clinical Diagnosis DIP joints, or “Bunions” in the Toes) - Joint Aspirate & Microscopy *(Needle-Shaped Monosodium- Diagnosis: Urate Crystals) - Normal Bloods - Imaging – (Narrowing Joint Space, Treatment: “Joint Lipping”, Ankylosis & Varus - Colchicine (For Acute Relief) Deformity) - Allopurinol (Preventative Only; Can Worsen an Acute Attack) Treatment: - NSAIDs - SIMPLE Analgesia (Panadol Osteo) - Corticosteroids - Surgery – (Joint Replacement / - Lifestyle Change ʹ (Avoid High-Purine Spinal Fusion) Foods (Meats, Fish, Beans, Peas, - Maintain Physical Activity Beer)) B. OSTEOARTHRITIS (Degenerative): Etiology - Degenerative Wear & Tear MODULE 3 – MUSCULOSKELETAL - Prepared by: Michael Angelo Sumugat RMT, MD 3  Pathophysiology Diagnosis: C. RHEUMATOID ;(AKA Seropositive͟Ϳ - Joint Aspirate + MCS. (Crystals?, ARTHRITIS (Commonest): Gram Stain?) - CBC (inc WBC) Etiology: - Inc ESR, CRP - Genetic Autoimmune - Endocervical/Urethral Swab or Urine PCR for Gonococcal. Pathogenesis: - Genetic (HLA-DR4 & -DR1 Genes) > Treatment: Rheumatoid Factor Production (Anti- - If Gonococcal – Azithromycin, IgG Ab) > Autoimmune > Ceftriaxone or Doxycycline Macrophage - Mediated Local Joint - If Staph – Ampicillin, Erythromycin Inflammation & Destruction or Vancomycin - Analgesia Morphology: - Arthroscopy – Aspiration & Washout - Erosion of the Articular Cartilage - (+/- Surgical Debridement/Joint down to the bone. Replacement) - Pannus - Inflamed thickened (NB: DO NOT USE Intra-Articular Steroids!!) hyperplastic synovium with papillary projections Complications: (NB: Normal synovium is very thin and - Avascular Necrosis of Femoral Head smooth and shiny) (if inc Intra-Articular Pressure due to - Fibrous Ankylosis (Bone Fusion) Pus) - Cartilage & Epiphyseal Destruction D. SEPTIC ARTHRITIS - Osteomyelitis (Bone Infection) Etiology OSTEOPOROSIS(“Porous Bones”) - Joint Infection Common causes – N.gonorrhoea, S.aureus, WHO definition - Osteoporosis͟ = A Bone Other less commons. Mineral Density of х-2.5 StDs below the Pathogenesis: mean BMD͟ - Routes of Spread – Hematogenous (Commonest), Direct from Adjacent NB: Osƚeopenia͟ = A BMD of between -1.0 Tissue, Iatrogenic. & -2.5 StDs below the mean BMD͟ Clinical Features – A Medical Emergency!: Etiology - (If Gonococcal > Preceding Bacteremia with Primary: Maculopapulovesicular Skin Lesions & Migrating Polyarthritis > Settling a. Type 1: Postmenopausal into Monoarthritis – Typically Knee) Osteoporosis (Typically Vertebrae & - Typically Severe Mono-Arthritis. NOF; females only) (Joint often held in slight flexion to o Decreased Estrogen > dec. Pain) Increased Osteoclast Activity o Swelling o Erythema b. Type 2: Or Senile Osteoporosis o Hot - (Affects all bones, males & o Dec. ROM due to Pain females)Decreased replicability or - + Fever + Malaise synthetic ability of the Osteoblasts > - (+/- Signs of Acute Sepsis – Fever, decreased Osteoblastic activity Chills, Dehydration, Lethargy) MODULE 3 – MUSCULOSKELETAL - Prepared by: Michael Angelo Sumugat RMT, MD 4  Pathophysiology - Used only for Post-Menopausal Secondary: Women - Endocrine - Cushing’s inc PTH͕ hyper b. Z-Score = Pts BMD Vs Age-Matched ͘ or hypothyroidism; DM͕ Acromegaly, Mean BMD Addison’s - Used only for people inc. Bone - TSH Level (Exclude Hyperthyroidism) Resorption > Porous Bones and Dec. Bone Mass (Bone Mineral Treatment & Prevention: Density) Pharmacological: Morphology: - **Bisphosphonates (Eg. Alendronate - Trabeculae are Thinner & Fewer [Fosamax], Risedronate) – (Monthly than Normal Dose) - Strontium > (Stimulates Ca- Clinical Features: Deposition & Inhibits Bone Resorption) Symptoms: - +/- Hormonal ʹ (SERMS (Eg. - Often Asymptomatic until Fracture. Raloxifene) or HRT (If Perimenopausal/Post-Menopausal)) Complications: - OTC Supplements ʹ (Calcium & Vit D) a. Fragility fractures ʹ (= Fractures - Occupational (Reduce Falls Risk, from minimal trauma ʹ E.g. From ↑Weight-Bearing Exercise) standing height) - NB: Rel-Risk DOUBLES with every 1.0 St. Deviation Below the Mean!! OSTEOMYELITIS - ( Spinal Cord Compression, Cauda Equina Syndrome Pathogenesis - Bacterial – S. aureus (Commonest), Investigations: Pseudomonas (Iatrogenic), H. influenzae - (Plain X Ray) (Children) - DXA (Dual-energy X-ray Absorptiometry) Bone-Mineral Morphology: Density Scan: - Macro: Local Swelling & Redness **ESSENTIAL: Lumbar Spine + Hip - Micro: Medullary Inflammation & *OPTIONAL: Forearm edema Interpretation of T-Scores & Z-Scores: Clinical Features: - History of Infection @ Another Site + a. T-Score = Pts BMD Vs Young-Normal ͘ Direct Trauma to the Area BMD MODULE 3 – MUSCULOSKELETAL - Prepared by: Michael Angelo Sumugat RMT, MD 5  Pathophysiology - Local Tenderness͕ and swelling Heat at Metaphysis and dec. ROM ͘ - (+ Signs of Acute Sepsis – Fever, Chills, Dehydration, Lethargy) Diagnosis: - Blood – inc. ESR͕, inc. WBC͕ inc CRP͕ Positive Cultures - X-Ray – Normal if Acute; radiolucency after 2-4 weeks; - Onion-Skin͟ Appearance if Chronic - CT/MRI – Medullary Oedema, Cortical Destruction & Articular Damage. Treatment: - Long Course IV Antibiotics (4-6wks) ʹ Rifampicin / Erythromycin / Tetracycline / Vancomycin - Irrigation/Debridement/Amputation - Replacement of Affected Prostheses *******END OF MODULE 3******** MODULE 3 – MUSCULOSKELETAL - Prepared by: Michael Angelo Sumugat RMT, MD 6  Pathophysiology Etiology: MODULE 3 OUTLINE - Decreased Production (Fe/Folate/B12 I. Disorders of the Red Blood Cell Deficiency Inc. Pernicious/Chronic a. Anemia Disease/Aplastic) i. Anemia secondary to Malnutrition - Blood Loss (Hemorrhage 1. Iron deficiency /Hookworm/Menorrhagia) anemia - Destruction/Abnormality of RBCs 2. Vitamin B12 anemia ERYTHROPOIETIN Hemolytic/ Microangiopathy ii. Anemia secondary to /G6PD/Sickle/Thalassemia/ increased destruction Spherocytosis) iii. Anemia secondary to chronic diseases - Spurious (Increased Plasma Volume – iv. Anemia of other causes Eg. Pregnancy/Fluid Overload) 1. Anemia secondary to increased blood loss Morphologies: (acute) II. Bleeding Disorders and Evaluation Size Classifications: a. Causes of Bleeding Disorders i. Thrombocytopenia a. Microcytic: Small - Reduced MCV ii. Defective platelet function b. Normocytic: Normal MCV iii. Von Willebrand’s disease c. Macrocytic: Large – Increased MCV iv. Coagulopathy v. Vascular causes Staining/Color: III. Disorders of the White Blood Cells Normal RBCs stain well – (Normochromic) Anemic a. Leukemia cells stain lightly - (Hypochromic) DISORDERS OF THE RED BLOOD CELL – ANEMIA A. Anemia of Malnutrition General: IRON DEFICIENCY ANEMIA (Microcytic Definition = “Decreased hemoglobin Anemia) concentration in blood” - May be Low Hb - (Most common type of Anemia) - OR low Hematocrit/Packed Cell Volume. Anemia = generally less than 100g/L Etiology: Normal Hb Range: - Chronic blood loss > MOST common cause of Iron Deficiency - (Normal Hb Concentration depends on (Eg. Parasitic Worm Infestation, age/sex/geographical location.) Malignancy, Menorrhagia, GI Ulcers) - 13 - 16g/dl (male) (130-160g/L) - Increased Need (Over-Demand): 11.5 - 16g/dl (Female) (115-160g/L) Pregnancy, Rapid Growth (children) - Poor diet / poor absorption: Malnutrition (↓Greens & Meat) [MODULE 4 – HEMATOLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 1  Pathophysiology Malabsorption, intestinal surgery, *Koilonychia (Spoon Nails) gastric atrophy. * Brittle Nails, Brittle Hair Pathogenesis: Diagnosis: - Iron is a fundamental constituent * Blood Count & Film (Microcytic, Hypochromic, of Hemoglobin Poikilocytosis, Anisocytosis, Pencils) - Therefore Iron deficiency > ↓Hemoglobin Iron Studies Synthesis (&↓RBC Production)à Anemia. (↓Ferritin; ↓Iron; ↑TIBC) Morphology – Blood Film: Treatment: Iron Supplementation - Microcytic (↑Divisions of Progenitors) (↓MCV) B. Anemia of Malnutrition: - Hypochromic (↑Central Pallor of RBCs) MEGALOBLASTIC ANEMIA/ (↓Hb Content) VITAMIN B12 DEFICIENCY - + An-Isocytosis (variations in size) ANEMIA/PERNICIOUS ANEMIA - + Poikilocytosis (Variations in shape (Macrocytic Anemia) - + Some “Pencil Cells”. (RBCs with one Sharp Edge) nd - (2 most common type of anemia) - (“Megaloblasts” = large, Erythroblasts with Clinical Features: Immature Nuclei - seen in the Marrow) Symptoms & Signs: Vitamin B12 Deficiency General Anemia Symptoms: Possible causes: Fatigue, Headaches & Faintness Exertional Dyspnea - Malnutrition – Lack of VB12 Dietary Exertional Angina Intake. Intermittent Claudication - Gastric – Deficiency of Intrinsic Factor (Incl. Exacerbations of CVS/Resp problems (Eg. Pernicious anemia – autoimmune in Elderly – Eg. Claudication & Angina) response to parietal cells of stomach↓IF↓VitB12 Absorption) General Anemia Signs: - Intestinal – eg. Resected Ileum/Crohn’s Pallor (Mucosal/Facial/Palmar Crease) Disease Tachycardia Systolic Flow Murmur (Hyperdynamic Folate Deficiency Circulation) Possible causes: Cardiac Failure (Eg. Pedal Oedema) -Malnutrition – Lack of Folate Dietary Signs Specific to Iron Deficiency Anemia: Intake (All due to cytochrome oxidase functional - Malabsorption – eg. Coeliac deficiency – Which requires iron to work) Disease/Intestinal Resection **Atrophic Glossitis (Atrophy of Papillae of - Excess Utilization – eg. tongue) Pregnancy/Lactation/Chronic *Angular Cheilitis/Stomatitis Inflammation/ Cancer [MODULE 4 – HEMATOLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 2  Pathophysiology - Excess Urinary Loss – eg. Acute Liver - Bone Marrow Biopsy (Shows Disease / Congestive Heart Disease Megaloblasts) – Rarely Required - Other General Causes: - Serum B12/Folate (↓ if B12/Folate Alcoholism (or Liver Disease) § Cytotoxic Deficiency) Chemo Drugs Old Age Treatment: - Oral B12 Pathogenesis - Oral Folate - VitB12/Folate are Necessary for Nuclear DNA - Corticosteroids + B12 Supplements (If Synthesis > defective nuclear maturation of Pernicious Anemia) erythroblasts > reduced RBC Production C. Anemia of secondary to increased Morphology: destruction: Marrow Biopsy: HEMOLYTIC ANEMIA - Megaloblasts in Bone Marrow (large, What is it? Erythroblasts with Immature Nuclei) - Anemia due to Increased/ Abnormal / Premature - Blood Film: RBC Destruction o *Normochromic o *Oval Macrocytes (Large, Oval Etiology (Refer to PowerPoint): RBCs o *Hyper segmented Neutrophils a. Intravascular Hemolysis: Occurs within the (Some with >6 Lobes in Nucleus) Circulation. o *Pancytopenia (Reduction in b. Extravascular Hemolysis: Occurs in the Number or ALL Cells – Reticuloendothelial System RBCs/WBCs/Platelets) (Liver/Spleen/Marrow) Pathogenesis: * Attempted ↑↑Erythropoiesis: ↑Reticulocytes - Breakdown of RBCs due to any cause > - Some “Polychromatophils” (Bigger, Release of Free Hemoglobin in Plasma. Blueish RBCs) - > Heme Molecule > Protoporphyrin & - Some Nucleated RBCs Iron - > ProtoporphyrinàExcess Bilirubin - + An-Isocytosis (variations in size) ↑Bilirubin (Unconjugated) > Jaundice - + Poikilocytosis (Variations in - > Bilirubin Conjugated in Liver > shape) Excreted in Bile & Feces. Clinical Features: Clinical Features: General Anemia Symptoms & Signs Symptoms: Investigations: - General Anemic Symptoms & Signs + - Blood Film (Oval Macrocytes, Symptoms Specific to Hemolytic Hypersegmented Neutrophils, Anemia: Pancytopenia) - CBC (↑MCV, Pancytopenia) Jaundice (Mild & Fluctuating) Splenomegaly [MODULE 4 – HEMATOLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 3  Pathophysiology Pigment Gall Stones (If Chronic HA) Venous Stasis Ankle Ulcers (Sickle Cell) D. Von Willebrand’s Deficiency: Microangiopathy/ Infarction/ - Either Not enough vWF....or Dysfunction of Raynaud’s vWF. - vWF is necessary for platelet adhesion. Laboratory Evaluation: - Therefore Deficiency > Poor platelet plug formation - Elevated Free-Hb in Blood (Hemoglobinemia) E. Coagulopathy = Defective Coagulation: - Hb in Urine (Hemoglobinuria)àRed- - Bleeding disorders due to Brown Urine. deficiency in 1 or more Coagulation - Hemosiderin (iron from Hb) in Urine Factors (Hemosiderinuria) - LFTs – (↑Bilirubin, ↓ Haptoglobins) Hereditary Coagulopathies: - Blood Smear – (Broken RBCs, Reticulocytosis, Congenital RBC 1. Hemophilia A: Factor VIII Deficiency: Disorders, Anemia) - Most common - Coombe’s Test – (?Autoimmune - Sex Linked Recessive (Female Carriers; Hemolytic Anemia) Affected Males) - Treatment - Recombinant clotting BLEEDING DISORDERS AND EVALUATION factors 2. Hemophilia B: Factor IX Deficiency: There Are Many Potential Causes Of Bleeding - AKA. Christmas Disease Disorders - Less common - Sex Linked Recessive (only affects A. Vascular Disorders: males) - Abnormalities in Blood Vessel Structure - Treatment - Recombinant clotting or Perivascular Connective Tissue factors Leads to: Easy Bruising 3. Other deficiencies (Factors V, VII, X, XI & XIII) Rare. B. Thrombocytopenia: - Just know they exist. - Due to deficient number of platelets. - Results from either: Acquired Coagulopathies: o ↓ Platelet Production o ↑ Platelet Destruction 1. Vitamin K Deficiency (Factors II,VII, IX, X) o ↑ Platelet Consumption (in large Dietary injuries/burns) Malabsorption C. Defective Platelet Function: Or Long-term warfarin - There are enough platelets, but not working 2. Chronic Liver Disease: properly. o May be Inherited (rare)...OR - Eg. Billiary Obstruction: - Acquired: (eg. From Aspirin/other blood - Hinders absorption of Fat-Soluble thinners) vitamins [MODULE 4 – HEMATOLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 4  Pathophysiology - Reduced synthesis of Factors II, VII, IX & - Time taken for plasma to clot after X addition of tissue factor (Factor III) - Eg. Severe Hepatocellular Damage: - Measures Extrinsic Pathway + part of o Reduced synthesis of Factor V & Common Pathway Fibrinogen - Measures factors VII, X, V, II 3. DIC - Disseminated Intravascular Coagulation: (Prothrombin) and I (fibrinogen). - AKA. Consumptive Coagulopathy - Normally 12-15sec. - Formation of small clots inside blood - 15sec+ = One/more of above factors are vessels throughout the body. deficient. - INR (International Normalized Ratio) is - Leads to: ↑Consumption of Platelets & derived from PT (Universal Coagulation Factors. measurement) c. Activated Partial Thromboplastin Time Evaluation of Bleeding Disorders: - Platelet Count (aPTT): - Literally the number of platelets/volume of blood - Time taken for plasma to clot after - Normal range = 150-400x10 /L 9 addition of phospholipids - Excessively Low platelet count > - Measures Intrinsic Pathway + the Thrombocytopenia (bleeding disorder) Common Pathway - Measures factors XII, XI, IX, VIII, X, V, II 1. Platelet Function Tests (Prothrombin) and I (fibrinogen). - Complete Blood Count (CBC)/Full Blood - Normally 25-45sec. Evaluation (FBE): - 45sec+ = One/more of above factors are - Include platelet count & morphology.- deficient. eg. Giant platelets 2. Bleeding Time d. Thrombin Time: - Time taken for wound to clot - Measures how quickly Thrombin is - If bleeding time is high > may suggest being activated. platelet dysfunction. - Time taken for a clot to form, following - If bleeding time is high, but normal addition of animal Thrombin. § platelet level > May be due to vWF Measures: Deficiency. - The conversion of Fibrinogen à Fibrin. 3. Platelet Aggregometry - Any deficiency of fibrinogen - Measures platelet aggregation with - Any inhibition of thrombin. common hemostatic agonists o ADP DISORDERS OF THE WHITE BLOOD CELLS - o Epinephrine LEUKEMIA o Collagen What Are Leukemias? - Measures the decrease in optical density that occurs in solution as - Myeloproliferative & platelets aggregate. Lymphoproliferative Disorders 4. Tests of Coagulation-Factor Function: a. Prothrombin Time (PT): [MODULE 4 – HEMATOLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD 5  Pathophysiology - A Type of Cancer Caused by Unregulated Proliferation of Abnormal ‘White Cells’ from a Mutant Type of Distinguishing Feature Hematopoietic Stem Cell. Leukemia - Successive generations of cells from that ALL – Acute Children Mutant HSC à “Clonal Expansion” Lymphoblastic Good Prognosis - NB: Disease occurs when sufficient Leukemia Small Lymphoblasts, Small Cytoplasm, No Granules/Nucleoli excess in Leukocytes. AML – Acute Adults Mutation – Genetic Alteration within a Single Myeloid Poor Prognosis (2mths if untreated) Myeloid OR Lymphoid Tissue Progeitor. Leukemia Gum Hypertrophy “Auer Rods” in AML Myeloblast Cells a. Chromosomal Translocations: Big Myeloblasts, Big Cytoplasm, - *Philadelphia Chromosome: Granules, Nucleoli. #1 Cause of *CHRONIC MYELOID CLL – Chronic Elderly LEUKAEMIA Lymphocytic Commonest Leukemia Insidious Onset b. Chromosomal Deletions/Additions: Leukemia Good Survival (9yrs) but NO Cure *Monosomy 7: #1 Cause of *ACUTE “Smear Cells” on blood film MYELOID LEUKAEMIA c. Point Mutations CML – Chronic Adults d. Gene Amplification: Myeloid Philadelphia Chromosome in 80% - Changes in Proto/Anti-Oncogenes: Leukemia Good Prognosis with Glivec (Imatinib) o Oncogenes: Code for proteins 3 Phases: Chronic, Accelerated, Blast Crisis. Marked Splenomegaly involved in cell proliferation/differentiation. o Abnormal Proto/Anti-Oncogenes Risk Factors: - Radiation Exposure – Nuclear/X- Cancers (ie. Leukemia) o Eg. A Hypermorphic Mutation in Ray/Microwave an Oncogene à Hyperactive - Previous Chemotherapy – Particularly Proliferation Alkylating Agents - Genetic – eg. Down’s Syndrome o Eg. A Hypomorphic Mutation in a Tumour-Suppressve Gene à - Occupational Chemical Exposure – Hyperactive Proliferation Benzene/Other Aromatic Organic Solvents - Viral Infection Result: Classifications of Leukemia: - Extreme numbers of White Cells in (NB: Myeloids are ALWAYS in Adults; Lymphoids are blood > Altered Hematocrit: EXTREMES of Age) - Huge Buffy Coat (of WBCs – generally abnormal) (All are ~Good Prognosis EXCEPT AML) - Low Proportion of RBCs (Results in (CML = Philadelphia Chromosome & Tri-Phasic with anemia) “Blast Crisis”) ********END OF MODULE 4******** [MODULE 4 – HEMATOLOGY] Handout Prepared by: Michael Angelo Sumugat RMT, MD