QUIZ 1 CONTENT 3 - Clinical Examination, Immune System - PDF

Examples of diseases predilection to certain gender More common In Male More common In Female 1 Coronary heart disease. 1 Systemic lupus erythematosus (More than 90% of cases of SLE occur in women, frequently...

Examples of diseases predilection to certain gender More common In Male More common In Female 1 Coronary heart disease. 1 Systemic lupus erythematosus (More than 90% of cases of SLE occur in women, frequently starting at childbearing age). 2 Peptic ulcer & Cancer stomach. 2 Thyroid disorders (thyrotoxicosis & Myxedema) 3 Bronchogenic carcinoma. 3 Bronchial adenoma 4 Hemophilia. 4 Gall bladder diseases (e.g. gall stones). 1/13/2025 5 Patients may be exposed to diseases due to certain occupations Occupation Diseases 1- Lead poisoning (plumbism): (Anemia- 1- Lead workers. Nephropathy- Hypertension- Muscle and joint pain- Mood disorders- Headache- Infertility). 2- Glass workers. 2- Silicosis ~ (Interstitial pulmonary fibrosis). 3- Radiologists 3- Bone marrow depression –(sterility). 4- Asbestos workers. 4- Asbestosis: (interstitial pulmonary fibrosis, bronchogenic carcinoma). 5- Aniline dyes. 5- Cancer urinary bladder. 1/13/2025 7  True or false question Conduct of clinical examination Privacy of examination: provide chaperones where appropriate. Room: should be well equiped to perform examination. The height of the examination couch or bed should be adjustable, with a step to enable patients to get up easily. Temperature: to be comfortable (warm). Noise: Control noise level and other distractions (phones). Illumination: should be sufficient light source and well lit (subtle abnormalities of complexion, such as mild jaundice, are easier to detect in natural light.). Seek permission and sensitively, but adequately, expose the areas to be examined, but avoid unnecessary exposure and embarrassment;. Cover the rest of the patient with a blanket or sheet to ensure that they do not become cold. Avoid exhaustion of the patient due to prolonged physical examination or frequent change in positions. Remain gentle towards the patient at all times, and be vigilant for aspects of the examination that may cause distress or discomfort. Acknowledge any anxiety or concerns raised by the patient during the consultation. Sequence for performing a physical examination The extent of the examination will depend on the symptoms that you areKnow investigating and the the de nition circumstances of the encounter. There is no single correct way to perform a physical examination but standardized systematic approaches help to ensure that nothing is omitted. Broadly speaking, any systematic examination involves the following: 1. Inspection: looking at the patient (for color changes, scars, abnormal breathing or pulsation patterns). (see) 2. Palpation: laying hands on the patient to palpate (feel). The structured approach to 3. Percussion: (tapping on the body) (tap) the examination 4. Auscultation: using a stethoscope to listen to the (hear) relevant system. inspection palpation percussion auscultation Gait and Posture Examination of the gait and posture Observe how the patient walks, If patients are ambulant, watch how they rise from a chair and walk towards you. Are they using a walking aid? Is the gait normal or is there evidence of pain, immobility or weakness? Note the patient’s preferred posture; whether the patient is restless or quiet. Observe for any apparent involuntary motor activity or immobility of the limbs. Aabnormalities of gait Abnormalities of gait can be pathognomonic signs of neurological or musculoskeletal disease: Hemiplegic gait: after stroke. Ataxic gait of diffuse cerebellar disease. examination of gait - Search Videos (bing.com) The walk of little steps it in Parkinsonism. Abnormal movements Tremor (in alcohol withdrawal). dystonia (perhaps as a side effect of neuroleptic therapy) Chorea (jerky, involuntary movements, characteristic of Huntington’s disease). Posture (position of the patient) Some patients suffering from certain diseases preferer certain positions POSITION DISEASES 1-Orthopnea position: shortness of 1-Left sided heart failure, mitral breath (dyspnea) that occurs when lying flat. stenosis , and tense ascites 2- Squatting position: 2-Fallot's tetralogy. 3.- Opisthotonus position 3.- Meningitis. hyperextension of the neck and spine together with flexion of the knee. 4- Flat in bed supporting the abdomen 4- Peritonitis with both hands, flexion of knee Hands examination: Nails The nails can be affected by both local and systemic disease and skin diseases & dermatophyte infection/onychomycosis (fungal infection), Psoriasis, Eczema, Lichen planus Beau’s lines: horizontal ridges/indentations in nail plate in all nails; typically follow a systemic illness due to growth disturbances. Koilonychia: spoon-shaped nail plate deformity in iron deficiency Clubbing: early stages - the angle between the proximal nail and nail fold is lost., there may be swelling of the distal digits or toe in later stages. Causes: bronchogenic carcinoma, suppurative or fibrosing lung disease, cyanotic congenital heart Examples of nail changes in systemic disease. A Normal nail. B Beau’s line. C Koilonychia. D and E disease, infective endocarditis, inflammatory Digital clubbing. bowel disease; rarely, familial or idiopathic. Hands examination: Skin of the hand examination Examination of the skin is part of general survey: Inspect hands for discoloration such as cyanosis, jaundice and pallor, pigmentation, scars, nevi/melanoma/ lumps noting their location and dimensions. Skin changes in the hands can indicate systemic disease, as: 1. coarse skin and broad hands of a patient with acromegaly. 2. tight, contracted skin (scleroderma). 3. calcium deposits associated with systemic sclerosis. Clues about lifestyle can also be seen in the hands: manual workers may have specific callosities due to pressure at characteristic sites, while disuse results in soft, smooth skin. Vital signs - Temperature Normal body temperature is [36.8 ±0.4 ºC] Fever means temperature more than 37.2 ºC AM or > 37.7 ºC PM. Hypothermia means temperature is 35 ºC or less Hyperthermia means temperature is 41 ºC of more Temperature-pulse dissociation (Relative bradycardia): For any increase in body temperature by one degree, there is an increase of pulse rate (10 beats/ minute) “Liebermeister’s rule”. However, the unusual pairing of fever with bradycardia is called “Faget's sign” usually seen in: a. yellow fever b- typhoid fever c-Brucellosis. c- brain abscess. D. COVID 19 Omicron d. Tularaemia. Common Causes of hypothermia: Common Causes of hyperthermia or (temperature is 35°C or Less) hyperpyrexia: (temp. is 41°C or more) 1--Cold weather. 1~ Heat stroke. 2~ Hypothyroidism. 2~ Thyrotoxic crises 3~ Adrenal insufficiency 3~ Pontine hemorrhage** 4~ Hypoglycemia. 4~ Status epilepticus*** 5~ Alcohol toxicity*. Q. Which of the *Alcohol (ethanol) is a CNS depressant. following is a common causeand Large amounts consumed rapidly can cause respiratory depression, coma, of hypothermia death. / hyperthermia Large amounts chronically consumed damage the liver and many other organs.  Types of Fever [fever is a temporary rise in body temperature] a- Sustained fever:- (nearly fixed fever) Know the types & de nition -Where the temperature remains above normal throughout a 24-hour period and does not fluctuate more than 1° Celsius in 24 hours. occurs in 1- lobar pneumonia. 2-urinary tract infection. b- Remittent fever: The temperature remains above normal throughout the day and fluctuates more than 2° Celsius in 24 hrs. occurs in 1-Tuberculosis (TB). 2-Typhoid fever. c- Intermittent fever: (Fever for some hours and normal other hours of the day).-In a 24 hours period the above normal temperature is only present for some hours of the day and the rest of the time is normal. occurs in 1-Malaria. 2- Septicemia* d- Cyclic fever (periodic or relapsing): (Fever on some days and normal other days). Occurs in bouts of several days alternating with afebrile periods. occurs in 1-Malaria. 2- Infectious Mononucleosis** Vital signs - Pulse The normal heart rate (HR) at mental and physical rest is 60-90/minute; but 90-100/min is considered a high normal pulse. The increased pulse rate is called tachycardia and the reduced pulse rate is called bradycardia. Sympathetic drive (to maintain Cardiac output) as COP = stroke Volume x Heart rate Tachycardia (Rate > 100 beats/m) Bradycardia (Rate < 60 beats/m) Causes of sinus tachycardia Causes of sinus bradycardia 1- Physiological e.g. stress. 1- Physiological e.g. sleep 2- Drugs: e.g. Sympathomimetic (Salbutamol). 2- Drugs e.g. Digoxin and beta Blockers. 3-Thyrotoxicosis (hyperthyroidism) 3- Hypothyroidism. 4- Severe anemia. 4- Obstructive jaundice. 5- Heart failure (HF). 5- Increased Intracranial tension (ICT) Vital signs – Respiratory rate Common terms in respiration Lenia rate of breathing is less than 10 breaths/min. Bradycardia: Tachypnea: rate of breathing greater than 20/min. Hyperpnea: inspiration are increased in depth and rate. Apnea: respiration ceases for several seconds. Hyperventilation: rate and depth of respiration increases. Hypoventilation: rate and depth of respiration decreases  Know the di erence between The immune system innate & adaptive The immune system has evolved to identify and destroy pathogens while minimizing damage to host tissue. More recently, it has become clear that the immune system not only protects against infection but also regulates tissue repair following injury and when dysregulated, governs the responses that can lead to autoimmune and auto-inflammatory diseases. Dysfunction or deficiency of the immune response can lead to a wide variety of diseases that may potentially involve every organ system in the body. Functional anatomy of immune system The immune system consists of an intricately linked network of lymphoid organs, cells and proteins that are strategically placed to protect against infection. Immune defenses are normally categorized into the innate immune response, which provides immediate protection against an invading pathogen, and the adaptive or acquired immune response, which takes more time to develop but confers exquisite specificity and long-lasting 3 protection. 1/25/2025  Innate defenses against infection include anatomical barriers, phagocytic cells, soluble molecules such as complement and acute phase proteins, and natural killer cells 1. Physical barriers 2. Phagocytosis 5 3. The Complement system 1/25/2025  Cells of innate immunity Neutrophils Neutrophils (polymorphonuclear leucocytes), PMN, are derived from the bone marrow and circulate freely in the blood. They are short-lived cells with a half-life of 6 hours, and are produced at the rate of 1011 cells daily. Their functions are to kill microorganisms, to facilitate rapid transit of cells through tissues, and to amplify the immune response non-specifically. Monocytes Monocytes are the precursors of tissue macrophages. They are produced in the bone marrow and enter the circulation. From the blood stream they migrate to peripheral tissues, where they differentiate into tissue macrophages and reside for long periods. Macrophages Specialized populations of tissue macrophages include Kupffer cells in the liver, alveolar macrophages in the lung, mesangial cells in the kidney, and microglial cells in the brain. 9 1/25/2025  3. Complement system Definitions The complement system comprises a group of more than 20 tightly regulated, functionally linked proteins that act to promote inflammation and eliminate invading pathogens by killing large numbers of bacteria and viruses on nucleated cells (it is the key host defence function in innate immunity). Complement proteins are produced in the liver and are present in inactive form in the circulation. Other functions of activated fragments of Complement: C3a –anaphylatoxin-release of histamine from mast cells & Basophils. C5a- chemotactic for macrophages and neutrophils, C3b- opsonization Complement Activation When the complement system is activated, it rapidly go on amplified biological cascade ends in a common pathway leads to the formation of multimolecular (C5b-9) membrane attack complex (MAC) which makes pores (holes) on the cell membrane of organisms /cells leading to their lysis. There are three pathways for activating complement cascade (chain reaction) and all converge on 11 activation of C3. 1/25/2025  Activation of complement pathways !!! C3 plays a pivotal role in complement activation through all three pathways. Know which binds to which The classical pathway: activated by binding of antigen–antibody complexes to C1, is blocked by C1 inhibitor (C1inh) Lectin pathway: mannose-binding lectins, which are macromolecules that bind to microorganisms, this activate the pathway by binding C4. in Alternative pathway: Bacteria activate the pathway through C3. 13 1/25/2025  The adaptive immune system Characteristics of adaptive immunity: 1. It has exquisite specificity and can discriminate between very small differences in molecular structure. 2. It is highly adaptive and can respond to an almost unlimited number of molecules. 3. It possesses immunological memory, and changes consequent to initial activation. Components of adaptive immunity: i. Humoral immunity involves the production of antibodies by B lymphocytes. ii. Cellular immunity mediated by the activated T lymphocytes, which synthesize and release cytokines that affect other cells, as well as directly killing target cells. 15 1/25/2025  Cells of adaptive immunity Mast cells and basophils Mast cells and basophils are bone marrow-derived cells that play a central role in allergic disorders Mast cells reside predominantly in tissues exposed to the external environment, such as the skin and gut, while basophils circulate in peripheral blood and are recruited into tissues in response to inflammation. Both contain large cytoplasmic granules that enclose vasoactive substances such as histamine. Mast cells and basophils express IgE receptors on their cell surface, which bind IgE antibody. On encounter with specific antigen, the cell is triggered to release histamine and other mediators that increases local blood flow and vascular permeability, stimulates smooth muscle contraction, and increases secretion at mucosal surfaces 16 1/25/2025  Cells of adaptive immunity Natural killer cells Natural killer (NK) cells are large granular lymphocytes that play a major role in defense against tumors and viruses. NK cells express a variety of cell surface receptor can recognize human leucocyte antigen (HLA) molecules allows it to remain tolerant to healthy cells but not to damaged ones. NK cells can also be activated by binding of antigen–antibody complexes to surface receptors. This physically links of the NK cell to its target antigen and known as antibody-dependent cellular cytotoxicity (ADCC). The activated NK cells can kill their targets in various ways: A. By secreting pore-forming proteins such as perforin into the membrane of the target cell. B. Secreting proteolytic enzymes called granzymes into the target cell, which cause apoptosis. C. Production of a variety of cytokines such as TNF-α and IFN-γ, which have direct antiviral and anti- tumor effects. 17 1/25/2025  Immunoglobulins: structure, classes and properties ─ Isotypes/classes of immunoglobulins are 5 types as determined by the type of heavy chain: IgG, IgM, IgA, IgE & IgD. There are also subclasses for IgG and A. IgM is the first antibody produced in infections (within 5-10 days) and is effective at agglutinating pathogens. It also activates the complement. IgG is the major antibody produced against infections and is found in the blood and extracellular fluid; can cross the placental barrier. IgG activates the complement; antibody appears later than IgM (1-2 weeks later). IgA is highly effective at neutralizing toxin and is important for mucosal surface defence. IgE is mostly bound to mast cell, basophils and eosinophils and is important in allergic reactions and defence against parasitic infection. IgD functions as a cell surface receptor. 23 1/25/2025  Immune deficiency Immune deficiency may arise through intrinsic defects in immune function but is much more commonly due to secondary causes, including infection, drug therapy, malignancy and ageing. The main consequences of immune deficiencies are : 1. The most useful indicator is recurrent infections (which is the main presenting problems): frequent/severe/unusual organisms/unusual sites. 2. Autoimmunity caused by failure of normal lymphocyte apoptosis. 3. susceptibility to malignancy. Types/causes of immune deficiencies Primary: due to intrinsic defects in immune function. Secondary: due to Infections, drug therapy, malignancy and ageing (more common type). 1/25/2025 29  Clinical staging & classification of HIV 1.World Health Organization (WHO) clinical stage: (used in low- and middle-income countries) Stage 1: Asymptomatic, Persistent generalised lymphadenopathy Stage 2: Stage3 Stage 4 (AIDS) 2.Centers for Disease Control (CDC) clinical categories: (used in high-income countries) Category A: Primary HIV infection, Asymptomatic, Persistent generalized lymphadenopathy Category B Category C (AIDS) Types and distribution of HIV HIV-1 is widely distributed, causes global HIV pandemic HIV-2: causes a similar illness to HIV-1 but progresses more slowly and is less transmissible, is restricted mainly to western Africa. 1/26/2025 41  Diagnosis and investigations Purpose of HIV testing 1. Identify infected individuals. 2. Educate patients about prevention and transmission of the virus. Pre- and post-test counselling is essential Screening tests: ELISA test: to detect p24 antigen, antibodies to both HIV-1 and HIV-2 (in order to detect patients with primary infection before the antibody response occurs). Two different immunoassays is sufficient to confirm infection. Confirmatory tests: 1. Western blot assays. 2. Nucleic acid amplification tests (PCR) to detect HIV RNA are used to diagnose infections in infants of HIV-infected mothers, who carry maternal antibodies to HIV. PCR is more sensitive than p24 antigen detection for 1/26/2025 diagnosing primary infection. 45  Viral load and CD4 counts 1. CD4+ count: it is the most clinically useful laboratory indicator of the degree of immune suppression. It is used, together with clinical staging, in decisions to start ART and prophylaxis against opportunistic infections, and in the differential diagnosis of clinical problems. The normal CD4 count is over 500 cells/mm3. The rate of decline in CD4 count is highly variable. People with CD4 counts between 200 and 500 cells/mm3 have a low risk of developing major opportunistic infections. Morbidity due to inflammatory dermatoses increasingly common as CD4 counts decline. 2. HIV viral load: it is a test to measure the number of HIV particles in a milliliter (mL) of blood. These particles are also known as “copies.” The test assesses the progression of HIV in the body and it is crucial for monitoring responses to ART. 1/26/2025 46  Clinical examination in HIV disease (SPECIFIC ORAL CONDITIONS) Oral hairy leucoplakia Corrugated white plaques running vertically on the side of the tongue Pathognomonic of HIV disease in a patient with HIV risk factors Asymptomatic; no treatment required Cause: EBV. High-dose aciclovir: to eradicate the infection Relapse: common 1/25/2025 58  Classification of hypersensitivity diseases 4 1/28/2025  Type I (immediate) hypersensitivity response (Allergy) Etiology: The increasing incidence of allergic diseases is largely unexplained, but one widely held theory is the ‘hygiene hypothesis’: This proposes that infections in early life are critically important in maturation of the immune response and bias the immune system against the development of allergies; Improvements in sanitation (hygiene) and health care decreased exposure to infection and results in the high prevalence of allergic diseases. Genetic factors: Can also contribute strongly to the development of allergic diseases - A positive family history is common in patients with allergy. 7 1/28/2025  Common causes of systemic allergic reactions Anaphylaxis: IgE-mediated mast cell degranulations. Anaphylaxis is a potentially life-threatening, systemic allergic reaction characterized by circulatory collapse, bronchospasm, laryngeal stridor, often associated with angioedema, and urticaria. The risk of death is increased in patients with pre-existing asthma, particularly if this is poorly controlled, and in situations where treatment with adrenaline (epinephrine) is delayed. 1. IV administration of drugs (penicillin, other antibiotics), antisera, IV anesthetic agents 2. Insect stings (Bee venom, Wasp venom) 3. Ingestion of certain foods (Peanuts, milk, eggs, soy products, fish and shellfish) 4. Chemicals – Latex. Anaphylactoid: Non-IgE mediated mast cell degranulation 1. Drugs: Aspirin and NSAIDs, Opiates, Radiocontrast media 2. Physical: Exercise, Cold. 3. Idiopathic: No cause is identified in 20% of patients with anaphylaxis. 8 1/28/2025  General approach to management of the allergic patient 1. Avoidance of allergen: This is indicated in all cases and should be rigorously attempted, with the advice of specialist dietitians and occupational physicians if necessary.. 2. Antihistamines: inhibit the effects of histamine, useful for prophylaxis against frequent attack. 3. Glucocorticoids: highly effective in allergic diseases, their adverse effects can be minimized by topical use. 4. Sodium cromoglycate : stabilizes mast cell membrane, effective as a prophylactic agent in asthma and allergic rhinitis, but it has no role in management of acute attacks or in food allergies. 5. Antigen-specific immunotherapy: This involves the sequential subcutaneous administration of increasing doses of allergen extract over a prolonged period of time. Highly effective in the prevention of insect venom anaphylaxis and in allergic rhinitis secondary to grass pollen. a) Omalizumab : Monoclonal antibody against IgE; it inhibits the binding of IgE to mast cells and basophils. It is used for urticaria and for severe persistent allergic asthma b) Adrenaline (epinephrine): Preloaded self injectable adrenaline may be life saving in acute 15 anaphylaxis. 1/28/2025  Know how Angioedema produced Pathophysiology Angioedema is the episodic, localized, non-pitting swelling of submucous or subcutaneous tissues. In most cases, the underlying mechanism is degranulation of mast cells (IgE mediated –allergic). However, angioedema may occasionally be mediated by increased local bradykinin concentration (Non IgE mediated/idiopathic; hereditary (HAE) –C1 inhibitor deficiency; ACE inhibitor associated). In hereditary angioedema (HAE), the angioedema may be spontaneous or triggered by local trauma or infection. The most important complication of HAE is laryngeal obstruction, often associated with minor dental procedures, which can be fatal. Types of angioedema: 1-Allergic reaction to specific trigger. 2- Idiopathic angioedema. 3- Hereditary angioedema. 4- ACE inhibitor associated angioedema 17 1/28/2025  Angioedema –Localized swelling of subcutaneous or submucous tissues (deep layers) 18 1/28/2025  Autoimmune diseases Autoimmunity is the presence of Immune reaction against self tissue (antigens). Autoimmune diseases: organ damage due to autoimmune reaction. These are a major cause of chronic morbidity and disability, affecting up to 1 in 30 adults at some point during life. Autoimmune diseases result from failure of immune tolerance, the process by which the immune system recognizes and accepts self-tissue. Clinical features: The clinical presentation of autoimmune disease is highly variable and span a spectrum: Localized (organ specific) or Systemic (non-organ specific) !!! Mechanisms of tissue damage: Hypersensitivity reactions types II, III & IV (except Type1) 29 1/28/2025  Etiology of autoimmune diseases Etiology: it is multifactorial- interaction of genetic, immunologic, hormonal (female) and environmental (infection, cigarette smoking, drugs), factors. Autoimmune diseases are much more common in women than in men, for reasons that remain unclear !!! Linkage to HLA class II antigens: – Many are associated with genetic variations in the HLA loci. (HLA genes are important in shaping lymphocyte responses). !!! Microbial agents in autoimmunity: Molecular mimicry: (e.g. rheumatic fever): antigenic similarities of streptococcal M protein and cardiac glycoprotein, Guillain–Barré syndrome and Campylobacter infection. Drugs: For example, autoantibodies /activated T cells directed against new antigens produced by binding of 32 metabolic products of drugs to cellular proteins 1/28/2025  Mechanism of tissue damage in autoimmune diseases and HSR 33 1/28/2025  Will give 4 choices and nd Autoimmune diseases: The spectrum /types which is speci c or systemic Organ-Specific Systemic Hashimoto thyroiditis Systemic lupus erythematosus Autoimmune hemolytic anemia Rheumatoid arthritis Autoimmune atrophic gastritis of pernicious anemia Sjögren’ syndrome Multiple sclerosis Reiter syndrome Autoimmune orchitis Inflammatory myopathies* Goodpasture syndrome Systemic sclerosis (scleroderma)* Autoimmune thrombocytopenia Polyarteritis nodosa* Insulin-dependent diabetes mellitus Myasthenia gravis Graves disease Primary biliary cirrhosis* Autoimmune (chronic active) hepatitis* Ulcerative colitis* 34 USMLE step 1Immunology (2008), Kaplan Medical 1/28/2025  Autoimmune diseases: Investigations Autoantibodies (ANA, dsDNA , Rheumatoid factor etc): used in the diagnosis and monitoring of autoimmune diseases. Measures of complement activation:– levels of C3 and C4 ; complement classical pathway activation leads to a decrease in circulating C4 levels and is often associated with decreased C3 levels. Cryoglobulins:- are antibodies directed against other immunoglobulins forming immune complexes that precipitate in the cold. Immune complexes can lead to type III hypersensitivity reactions, with typical clinical manifestations like purpuric rash, arthralgia and peripheral neuropathy 38 1/28/2025  Autoimmune disease: Management The management of autoimmune disease depends on the organ system involved. In general, treatment of autoimmune diseases involves the use of: 1. Glucocorticoids 2. Immunosuppressive agents, 3. Biologic agents: target disease-specific cytokines and their receptors. Increasingly used in combination with Immunosuppressive agents, 4. Others: Not all conditions require immunosuppression: For example, the management of coeliac disease (gluten hypersensitivity) involves the withdrawal of dietary gluten. Autoimmune hypothyroidism requires appropriate thyroxine supplementation. 39 1/28/2025