Respiratory System Final Notes PDF

The Respiratory System 1 Upper RT – Nose, sinuses, larynx, trachea, main bronchi Effected areas Nose Sinuses Larynx trachea Symptoms Mild/transient Cause...

The Respiratory System 1 Upper RT – Nose, sinuses, larynx, trachea, main bronchi Effected areas Nose Sinuses Larynx trachea Symptoms Mild/transient Cause Viral Lower RT – bronchi, lungs, terminal bronchi Effected areas Bronchi Terminal bronchi Lung parenchyma Symptoms Serious - mortality Cause 2nd to irritants Bacteria Viruses Atypical fungi Defence mechanism of respiratory organs: Cough reflex (aspiration) Nasal hairs Ciliary apparatus Secretion of IgA antibodies Phagocytic activity by alveolar macrophages Accumulation of secretions Alveolar fluid Cell mediated immunity (chronic diseases) Virulent infections Primary infections: Viral, bacterial, mycoplasma, fungal Secondary bacterial: following a viral infection. Secondary to irritants. Viral infections: Common cold: ○ Acute inflammation of eyes and throat with congestion and watery exudate ○ Secondary bacterial infection Viral sore throat: ○ Adenovirus (pharyngitis) ○ Secondary infection (purulent- pus) Influenza: ○ Involves mainly upper respiratory tract. Bacterial: ○ Streptococcus Pyogenes Acute laryngitis/ epiglottis: ○ Haemophilus influenza type B/ Streptococcus Pyogenes Pneumonia: ○ infection of alveolar spaces which generates a host reaction (alveolar exudates) ○ Complications: pleurisy Bronchopneumonia: Inflammation starts in the bronchus and spreads to adjacent alveolar spaces Streptococcus pneumoniae/ Staphylococcus Aureus White yellowish foci of condensation, separated by normal lung parenchyma. Lobar Pneumonia Streptococcus pneumoniae Inflammation starts in the alveoli and moves to the entire lobe. Congestion, red and grey hepatization. Viral pneumonia Interstitial pneumonia, initially atypical pneumonia. Influenza A + B, Adenovirus, SARS Pulmonary Tuberculosis- Mycobacterium tuberculosis Primary tuberculosis in childhood (rare)  Primary lesion (ghon focus- below pleura in mid lung, heal with fibrosis/ calcification) ○ TB survives in Foci and becomes the source of later infection. ○ Patient develops cell mediated immunity. Secondary tuberculosis: new infection or by reactivation of microbe ○ Coughing up caseous material provides a source of infection. __________________________________________________________________________________________ The Respiratory System 2 ‘Define chronic bronchitis and emphysema.’ ‘Discuss the pathogenesis of emphysema’ COPD Chronic bronchitis ○ Persistent cough with sputum production Emphysema ○ big weak air spaces which causes air to enter in chest cavity which can cause pneumothorax (enlargement of air spaces distal to the terminal bronchiole) ○ destruction of alveolar walls ○ pathogenesis: proteases/ antiproteases produce elastase. ○ Prognosis: with severe emphysema (cor pulmonale) death can occur. Both chronic bronchitis + emphysema are accompanied by obstruction to air flow. ‘Discuss the pathogenesis of asthma.’ Asthma Paroxysmal constriction of the bronchial airways. Bronchi are occluded by thick mucous plugs. Eosinophils in bronchial walls. Allergic asthma (type 1)- IgE  Occupational chemicals (type 1 and cell mediated)- after repeated exposure Type 1: activates mast cells and basophils hence it releases histamine (vasodilation) ‘Describe the classification of malignant lung tumours.’ Lung Tumours Epithelial (90-95%) ○ Non-small cell carcinoma (70-80%) Squamous cell: (25-40%) from smokers Arises in a main bronchus from squamous epithelium Large friable mass which extends into surrounding lung, main airways Adenocarcinoma: (25-40%) Peripheral tumours Originate from glandular epithelium Large cell (10-15%) Small cell carcinoma (20-25%) Oat cell Carcinoid Lymphoma ‘Discuss the incidence, cause and prognosis of primary lung carcinoma’ ‘Describe the spread of primary bronchial carcinoma.’ Bronchial carcinoma Incidence 40-70 yrs Cause Cigarettes Prognosis Poor surgical resection when practical possible in only 20 - 30% of patients 30-40% 5yr survival after surgery Spread and metastases Spread and ○ Local; lung, hilar tissues, large blood vessels. metastases: ○ Lymphatics: hilar first, cervical ○ Blood: liver, adrenal glands Non-metastatic systemic effects finger clubbing, cachexia, neurological syndromes Paraneoplastic Syndromes Paraneoplastic: hormone production ACTH / ADH / PTH Small cell or squamous cell Secondary- multiple nodules, any tumour, breast kidney and testicular tumours. Distinguish secondary lung tumours from primary lung tumours. Feature Primary Lung Tumors Secondary Lung Tumors Origin Arise from lung tissue or bronchi. Metastases from other primary cancers. Morphology Solitary mass; squamous, Multiple nodules scattered in adenocarcinoma, etc. the lungs. Common Primary Lung tissue itself. Breast, kidney, testis, etc. Sites Histology Differentiated lung-specific cell Histology matches primary types. tumor (non-lung). Prognosis Depends on type and stage. Reflects prognosis of primary tumor. Neoplasia: Definitions/nomenclature Neoplasia New growth - benign or malignant Tumor Benign or malignant Cancer Malignant Oncology Study of cancer Pathologist Studies disease Oncologist Treats cancer patients Benign (-OMA) Cannot metastasize but can still be lethal ex: CNS Malignant (-CARCINOMA) Tumour acquired ability to invade and spread Differentiation How closely cancer resembles original site of origin DESCRIPTIVE TERMS FOR MALIGNANCY Pleomorphism Varies in size and shape Mitotically active proliferates  Hyperchromasia Darker nuclei Anaplasia Wild appearance Cell types Epithelium Lining tissue Mesenchymal Bone, cartilage, muscle Germ cell Reproductive systems – testes, ovaries May be benign (cannot metastasis but can still be lethal) or malignant (can spread). Benign: suffix – oma - (Lipoma, chondroma, adenoma (gland) Benign vs malignant Benign Malignant/metastasis Cannot metastasize but can still be lethal Cancer spreads from original site of origin ex: CNS Ex: Lymphatic – carcinomas Blood – sarcomas Epidemiology - study of how often diseases occur in different groups of people and why 1. Environmental 2. Ageing population 3. Iatrogenic – chemotherapy related cancers Genetics – influences: 1. Balance between cell replication and cell death 2. Oncogenes vs tumour suppressor genes 3. Mutations a. Hereditary – family history b. Acquired – somatic i. Environment ex: sun ii. Occupation iii. Diet Mutations answer Point Change at point Deletions Deletion of part of gene Rearrangements Rearrangement of genetic material Amplification Increasing copy numbers Gain or loss of Gain of func – promote cell growth function Loss of function – promote cell death 4. Oncogenesis = mutations leading to cancer development Disorders of growth and differentiation Definitions of growth, differentiation, morphogenesis, cell turnover, apoptosis Growth Increase in cell size and mass Differenciation. Cell acquires specialist features Morphogenesis Embryonal development – organ formation Cell turnover Balance btwn growth vs apoptosis Apoptosis Programmed cell death – by endogenous endonuceleases (autodigestion) Regenerative capabilities of cells Labile High turnover + regeneration Stable Low tyrnover + high regeneration Permanent CANNOT regnerate – eg: neurons , brain injuries etc..) Cell cycle overview (brief) S phase DNA replication M phase Mitosis or meiosis G1 & G2 Synthesizes protein - G1 – determines how quickly it replicates Interphase Stage that’s NOT undergoing mitoses/meiosis Factors influencing growth (genetic, hormonal, environmental) Genetic Ex: chromosomal abnormlities Hormonal Insulin Environemntal Nutrition eg: postnatal nutrition Foetal growth (very brief) o Sex steroids pass over o High sugar levels cross over from mum – fetus makes insulin (growth hormone) o Smoking, alcohol, drugs – influence foetal growth Recap of tissue responses; hyperplasia, hypertrophy, atrophy, Atrophy; mechanisms Hyperplasia Increase in cell number hypertrophy Decrease in cell numner atrophy physiological or pathological - Decreased function – disuse - Loss of innervation - Loss of blood supply - Pressure atrophy - Lack of nutrition - Loss of endocrine simulation - Hypoplasia – just decreased growth – usually a failure of morphogenesis Differentiation; how does it come about? o Genetic – transcription transport, translation, transcriptional control Agenesis, atresia, hypoplasia, dysgenesis, ectopia Agenesis Failure of organ development Atresia Failure of development of lumen ex: osophagus Hyopoplasia Failure to reach normal size - organ dysgenesis persistence of embryonic structures Ectopia presence of mature tissue in an abnormal site Gastrointestinal tract Oesophagus Squamous cell carcinoma (diagnosis by biopsy) – Tobacco, alcohol etc.. Adenocarcinoma: 50% of oesophageal cancers arise due to GORD ( astro- oesophageal reflux disease), inflammation + ulceration Stomach Adenocarcinoma: caused by helicobacter pylori, AI gastritis Lymphomas: helicobacter Carcinoids - tumor secretes certain chemicals into your bloodstream, causing a variety of signs and symptoms Acute gastritis: superficial ulceration, caused by NSAIDs, asprin, Alcohol, smoking, chemotherapy, infections, stress Helicobacter gastritis: chronic gastritis (treat antibiotic) Peptic ulcer: treat with PPI GI Cancer type Caused by: Adenocarcinoma caused by helicobacter pylori, AI gastritis Lymphomas helicobacter Carcinoids tumor secretes certain chemicals into your bloodstream, causing a variety of signs and symptoms Acute gastritis superficial ulceration, caused by: - NSAIDs - Asprin, - Alcohol, - Smoking, - Chemotherapy, - Infections, - stress Helicobacter gastritis: chronic gastritis (treat antibiotic) Peptic ulcer: treat with PPI Small Intestine Adenocarcinoma Carcinoid tumours & lymphomas Malabsorption Ischaemia Large intestine Hyperplastic polyps: benign Adenomatous polyps: pre malignant Hamartoma: inflammatory Adenocarcinoma: excess energy intake and low fibre Inflammatory bowel disease ○ Ulcerative colitis and Crohn’s disease (in ileum) Ischaemic bowel disease ○ Lack of blood supply to bowel Diverticular disease ○ Distal colon as fibre decreases Liver Hep A: acute hepatitis, no chronicity Hep B: could lead to cirrhosis Hep C: could lead to cirrhosis Jaundice Bilirubin (produced in liver), if hepatocytes are not functioning it is retained and gives a yellow colour. Cirrhosis Results in hepatic failure as it is the result of continuous scarring of the liver. Scar tissue replaces healthy tissue in the liver and prevents liver from working. Tumours Hepatocellular carcinoma (association with Hep B) Cholangiocarcinoma (associated with gallstones in gallbladder) Pancreas Acute pancreatitis ○ Caused by: blockage in bile duct caused by gallstones, heavy alcohol use, high Ca in blood. ○ This causes autodigestion of pancreas by activated enzymes Chronic Pancreatitis  ○ A progressive inflammatory disorder that leads to irreversible destruction of exocrine and endocrine pancreatic parenchyma caused by atrophy (tissues are wasted away) and/ or replacement with fibrotic tissue. ○ Risk of carcinoma Carcinoma Islet cell tumours Adenocarcinoma of pancreas Gallbladder 80% cholesterol stones 20% pigment stones (bilirubin Ca salts) Cholecystitis (redness + swelling of gallbladder when bile is trapped inside normally as gallstones block the tube) ○ Associated with gallstones ○ Acute inflammation precipitated by obstruction of neck or cystic duct Acute inflammation After the inflammatory response des it job and there is wound heling Uses neutrophils which enable the immune cells to recognise the pathogen using Toll Like receptors. When cells are damaged they release more products which can be detected by inflammatory cells (cytokines). ○ Quickly go to the site of inflammation. ○ Have powerful enzymes which can degrade the microbes Abscess: collection of pus Ulcer: defect in surface of tissue (can heal by fibrosis) Resolution: ○ Heals by connective tissue replacement: fibrosis ○ Can proceed to chronic inflammation. ○ If it becomes unregulated it can kill; Causes Infections Trauma Tissue necrosis Immune reactions Foreign bodies Alteration to blood vessels Alter endothelial cells hence become more permeable so more proteins to the site hence, swelling occurs (oedema) as fluid accumulates Blood vessels dilate Exudate: fluid rich in proteins Transudate: fluid lower in protein concentration  Pus: purulent material laden with neutrophils, and cell debris Lymphatics Drain extravascular fluids and in turn can become swollen up (lymphangitis) Inflamed lymph node (lymphadenitis) Cancer: lymphangitis carcinomatosa Stages of Activation Inflammation occurs Alteration of blood flow (causes wbc to become closer to the vessel wall and attach) Redistribution of blood vessels (margination). ○ Selectins ○ Integrins Transmigration: Once wbc attaches and permeates through the cell wall. They are attracted to the area of interest via chemotaxis Killing pathogen ○ Phagocytosis ○ Oxidising agents: ROS = & Nitric oxide ○ Granules within enzymes How does it stop ○ Anti inflammatory agents- transforming growth factor B Mediators: (short lived and has an ability to stimulate other mediators) ○ At site: cell derived mediators ○ Mediators which circulate: plasma derived mediators ○ Histamine ○ Cytokines ○ Arachidonic acid (present in plasma membrane) Leukotrienes Prostaglandins which need COX to be produced Morphology Abscess: collection of purulent material Fibrinous inflammation: vascular leak and fibrous formation is marked Ulcer: defect in tissue surface (if chronic it heals by fibrosis) Resolution: Fibrosis Can kill you if unregulated as it develops into: ○ Sepsis ○ Anaphylactic shock Chronic Inflammation- cellular constituents Failure of acute inflammation, allergic reactions, prolonged exposure to the substance Differences between acute inflammation and chronic= 1. Different cell constituents 2. Some more tissue destruction 3. Seeing features of wound healing Cell constituents (mono) Macrophage (derived from monocytes) ○ Phagocytosis ○ Antigen presenting cell (stimulates T cells) ○ Secretes inflammatory mediators ○ Activated by microbial products/ cytokines Lymphocytes ○ T cells which when activated secrete more cytokines Plasma cells Mast cells ○ IGE mediators (anaphylactic reaction) Eosinophils : parasitic infections (have granules which are toxic to parasites) Granulomatous inflammation (seen in Tb, rheumatoid arthritis etc). can cause necrosis Collection of epithelioid histiocytes Bordered by lymphocytes May also be associated with giant cells Systemic responses of inflammation Fever: induced by pyrogens Prostaglandins: increase blood supply Leukocytosis: increase in wbc Breast Cancer Benign (the majority of lumps that one feels are benign) Fibroadenoma (mobile hence non fixed lumps) Fibrocystic disease Fat necrosis Cysts Involution (removes milk producing epithelial cells) Malignant Invasive ductal carcinoma Invasive lobular carcinoma Triple negative breast cancer (common in younger women) Screening 5-10% of breast cancers are genetic thus the majority are not genetic. A mutation in the BRCA ½ gene does not mean that breast cancer will evolve but it can increase the chance of getting breast cancer. Skin Tumours (most common) Epidermal Pre malignant: (treatment by freezing, excision and curettage) ○ Actinic Keratosis: sun exposed skin ○ Bowen’s Disorder: rarely evades but more aggressive Squamous Cell Carcinoma ○ Induction of p53 by sunlight/ chemical exposure/ renal transplantation/ HIV Basal Cell Carcinoma (treatment by radiotherapy & surgery) ○ Cytological similar to basal cells ○ Mainly sun exposed and commoner in immunosuppressed patients ○ Slow growing and invades locally Adnexal (vast majority are benign) Pilomatrixoma Melanocytes (mature melanin) Epidermal naevus: benign hamartoma present at birth or early childhood (tipo ta birthmark) Sebaceous naevus: yellow-orange hairless patch/ plaque (overgrown epidermis, sebaceous glands and hair follicles) at birth on scalp Connective tissue naevus: uncommon skin lesion that occurs when the deeper layers of the skin do not develop correctly looks like sebaceous These could also be separated into; ○ Spitz: benign dome shaped moles ○ Congenital: the moles are present since birth ○ Blue: benign skin lesions which have blue- black colours ○ Halo: mole which has white/ lighter coloured ring which is caused by an immune response as the body tries to attack it. ○ Neoplastic: can form malignant tumours ○ Dysplastic: can form benign tumours Malignant ○ Thin melanomas ○ Occur after puberty mainly ○ No metastatic potential ○ Biopsy should be performed Lentigo maligna melanoma ○ Sun exposed areas of elderly ○ When invasive, low aggression  ○ Desmoplastic: aggressive & difficult to diagnose Superficial spreading melanoma ○ In situ called pagetoid melanoma ○ Has elevated nodule Nodular melanoma ○ Invasive melanoma with no in situ phase (young age groups and more aggressive) Acral lentiginous melanoma ○ Palms, soles etc Prognosis ○ Using Clark’s system ○ Breslow thickness ○ Ulceration ○ Surgery Female Genital Tract Cervix Associated with HPV Genital warts Dyskaryosis (abnormal cell changes not cancer) Cervical intraepithelial neoplasia Squamous cell carcinoma Uterus Polyps Hyperplasia Fibroids ○ Leiomyomata ○ Benign Endometrial carcinoma Endometrial adenocarcinoma ○ Prolonged oestrogen stimulation + obesity ○ Abnormal bleeding Ovarian (Majority benign) Epithelial ○ Adenocarcinoma Germ cells ○ Teratoma Sex cord/ stromal ○ Fibroid  Olaf Woods Atherosclerosis, Ischaemia and Infarction Heart function: coordinating blood pump The heart does not regenerate The Circulatory System Right ventricle receives blood from right atrium and passes to pulmonary artery which passes the deoxygenated blood to the lungs. Pulmonary artery: pushes deoxygenated blood away from the heart to. the lungs. Pulmonary vein: pushes oxygenated blood to the heart from lungs to be pushed towards the whole body. Lymphatics Regulate: oncotic pressure and hydrostatic pressure in intestines Papillary muscles: attach with valves with tendons to prevent blood going upwards. Aortic + pulmonary valves have a fibrous ring only!! Purkinje fibres: electrical conduction in ventricles Arteriosclerosis Thickening, hardening and loss of elasticity of arterial walls which restricts the blood flow to the organs and tissues. Elastic arteries: aorta, iliac arteries Muscular arteries: coronary, carotid, cerebral arteries Arteriolosclerosis: Occurs in arterioles mainly due to hypertension and dm. Atherosclerosis Requires initial event such as chronic endothelial injury composed of a fibrous cap and an atheromatous cap. LDL will accumulate in the arteries, muscle cells will try to engulf them causing foam cells to form a plaque which is LDL covered by a fibrous cap. Ca will then form a plaque and then harden which forms complicated atheroma. LDL (cholesterol) is present in: macrophages, smooth muscle cells (body’s attempt to seal the damage) and extracellularly (cholesterol crystals). The inflammatory cells will then infiltrate the plaque and after becomes calcified. Effects: ○ Stenosis: narrowing of the arteries (leads to less blood flowing to the area, might not be always to arteries hence, even different areas) (causes ischaemia) ○ Ischaemia: poor blood flow (no death but injury) ○ Occlusion: complete blockage hence, death of tissue supplied (if ischaemia is not taken care of) ○ Infarction: death of tissue due to absence of blood Vulnerable Plaques: small fibrous cap, more dangerous as it can rupture (from ischaemia to infarction) but in stable a cap is hard hence it can’t rupture. Stable Plaques: large fibrous cap Histology There is a rupture from the macrophages and a thrombus is released consisting of fibrin, erythrocyte and platelets. Pathogenesis of Atheroma Injury to endothelium is caused by; haemodynamic stress, hypertension and toxic effects of LDL. This allows plasma lipoproteins to enter the arterial wall to be engulfed first by macrophages and later by smooth muscle cells. Risk factors: Non modifiable: ○ Gender ○ Family history of hyperlipidaemia ○ Race Modifiable: ○ High blood pressure – Diabetes mellitus ○ Smoking ○ Hyperlipidaemia ○ Obesity ○ Excess alcohol ○ Sedentary life ○ Stress and depression – Trauma Hyperlipidaemia (blood contains lipoproteins) 1. Chylomicrons- mainly triglycerides 2. VLDL- very low density lipoproteins 3. IDL- intermediate density lipoproteins 4. LDL- low density lipoproteins (cholesterol) 5. HDL- high density lipoproteins Primary Hyperlipidaemia Genetic Predisposition- polygenic High risk of developing atherosclerosis Develop xanthomas (development of fat under the skin) Treat with low LDL diet and drugs Secondary hyperlipidaemia Secondary to diabetes, renal disease, alcoholism, treatment with corticosteroids and hypothyroidism. Predispose to atheroma Consequences of Atheroma: Ischaemia: reduction of blood flow by narrowing of the arteries (critical lesion) Infarction: occlusion of blood vessels (bleeding plaque + atheroma) Thrombosis: (with embolization as a complication) Aneurysm: (weakening of the vessels) Ischaemia + Infarction Coronary Artery: (arteries which supply the heart) Stenosis: caused by atheroma and its complications lead to Ischaemic Heart Disease Myocardial infarction: cause by complete blockage Transmural infarct in the posterior wall of the left ventricle To cure artery + vein grafting is used (bypass). This can lead to cerebral infarction and acute intestinal obstruction. Thrombosis Thrombus: blood clot which occurs inside blood vessels, occurs as a coagulation system is activated and a mesh of platelets and fibrin hence, defects the vessel. In normal vessels this is prevented by fibrinolysis. Depends on: ○ endothelial dysfunction or injury: direct injury in trauma + inflammation/ haemodynamic stresses in vessels with atheroma ○ hemodynamic changes: hypertension/ stasis (immobility) ○ hypercoagulability: deficiency of protein C or S/ prothrombin mutations which leads to thrombosis. Sites: ○ Arteries: coronary arteries (usually occlusive), mural thrombi in aorta. ○ Veins: in deep veins of calf muscles ○ Heart: poorly contracting chambers, damaged heart valves Outcome: Dissolution by fibrinolytic mechanism ○ Propagation by enlargement ○ Organisation of growth of granulation tissue from vessel wall and recanalization of organised thrombus (restoring flow to interrupted channel). ○ Embolism: when fragments break off and are carried in the circulation to other vessels hence, the arteries get weaker so it turns into a capillary. Embolism A material within a blood vessel that is carried by the blood to a site distant from its point of origin (normally arises from a thrombus). Arterial embolism: travel through systemic circulation to lodge in multiple places within the body. May arise from: ○ Thrombi in heart ventricle ○ Thrombus in left atrium ○ Bacterial endocarditis (vegetation) ○ Plaques of atheroma  Pulmonary embolism: enlarge the veins of the calf muscles or pelvic veins. Cardiovascular System Ischaemic Heart Disease Poor blood supply Caused by atheroma (fat and scar tissues) of the coronary arteries Acute Coronary Artery Syndrome Functional disturbances on exercise Myocardial infarction (loss of cells, abnormal function of survivors) Sudden death Myocardial Infarction- an area of myocardial necrosis due to ischaemia (loss of cells because of insufficient blood supply) Caused by: Coronary artery being closed off Fall in blood pressure Complications: ○ Muscle damage ○ Disorderly contraction ○ Ineffective pumping action ○ Arrhythmia ○ Acute heart failure ○ Cardiogenic shock ○ Thrombus ○ Rupture of septum and papillary muscles ○ Pericarditis ○ Chronic heart failure ○ Dressler’s syndrome- know it exists Plaque is damaged by ulceration/ rupture which promotes a thrombus Fissures enable haemorrhage into plaque and angina becomes severe, an artery is then blocked which can cause arrhythmia. Survival- replacing dead tissue by fibrosis  Collateral- natural bypass Mitral competent or regurgitation Heart failure- heart fails to cope with increased demand (muscle hypertrophies- grows in size but then it dilates with declining contractility) Varicose vein- valves are dilated so back flow is prevented. Hypertension- blood pressure is sustained at a higher level than accepted (higher level than 90 diastolic) Arterial blood pressure: cardiac output x peripheral resistance Primary hypertension: abnormal transport of Na and K across cell membranes (without specific cause) Secondary hypertension: renal artery stenosis,, endocrine diseases and coarctation of the aorta, Conn’s syndrome (has underlying conditions) Consequences: cardiac output increases, left ventricle hypertrophies (cardiac failure), kidney damage, stroke and haemorrhage due to rupture of small vessels in brain, retinal exudates with arterial narrowing, David Busuttil Haemopoiesis Haemopoiesis- production of red blood cells which occurs in red bone marrow Stem Cell 1. Totipotent Stem Cells: These are the most potent stem cells and can develop into any cell type in the human body, as well as extraembryonic tissues like the placenta. Totipotent stem cells are present in the very early stages of embryonic development. 2. Pluripotent Stem Cells: Pluripotent stem cells are not as versatile as totipotent cells, but they can still differentiate into almost any cell type in the human body. Embryonic stem cells, which are derived from the inner cell mass of a blastocyst (a very early- stage embryo), are an example of pluripotent stem cells. 3. Multipotent Stem Cells: These stem cells are more specialised and can differentiate into a limited range of cell types. Multipotent stem cells are found in various tissues throughout the body, such as bone marrow, where they give rise to specific cell types like blood cells. 4. Unipotent Stem Cells: Unipotent stem cells are the most specialised and can only differentiate into a single type of cell. An example of unipotent stem cells is the myoblasts, which can only give rise to muscle cells. Function: WBC: immune system RBC: transporting oxygen Platelets: blood clotting Reticuloendothelial system: macrophage function Phagocytosis Immune surveillance Antigen presentation: present antigens to other immune cells Cytokine production: intercellular communication Tissue repair Homeostasis maintenance: by removing old/ damaged cells Erythropoietin Produced in the kidney to produce red blood cells and for the rbc to mature. Regulated by the oxygen content in the body. Porphyrins are needed to provide haem groups necessary for oxygen binding Red blood cells  Have a biconcave shape so more haemoglobin fits Its membrane is flexible and selectively permeable Anaemia: Lab diagnosis: ferritin (stores iron), serum iron (measures plasma), marrow iron stores Megaloblastic anaemia: deficiency of vitamin B12 + folic acid Aplastic anaemia: low rbc, wbc and platelets in blood (therapy, bone marrow transplantation) Microcytic anaemia: smaller than normal anaemia Anaemia of chronic disease: anaemia of inflammation Polycythaemia- abnormal increase of rbc Myelodysplastic syndrome: not enough production of healthy blood Marrow Infiltration- abnormal cells infiltrate the bone marrow (storage disease) Hydro deficiency anaemia Haemolytic anaemia Sickle cell anaemia- point mutation in haemoglobin and its shape is different hence more fragile and does not perfuse very well. Thalassemia: reduced production of one or more of the globin chains Hereditary- rbc become spherical hence, more fragile Idiopathic- cause not known Thrombocytopenia- low platelet Thrombocytosis- high platelet Acute leukaemia – stem cell produces blast cells (rapid uncontrolled growth of immature wbc) Chronic leukaemia- slower and gradual accumulation of mature but abnormal wbc. Myeloma- blood cancer that begins in plasma cells Lymphoma- blood cancer that begins in lymphocytes LEUKOCYTES 1. Neutrophils- multiplied nucleus and has granules (pale red and blue), its levels are raised when acute bacterial infections are present.  2. Eosinophils: bilobed nucleus and has cytoplasmic granules (red), its levels are raised when allergic reactions and parasitic infections are present. 3. Basophils: bilobed nucleus and has cytoplasmic granules which are histamine and heparin- blood clotting (purplish black), its levels are raised when inflammation occurs. 4. Monocytes: pale blue cytoplasm which when they move into tissues become macrophages and engulf bacteria and debris. 5. Lymphocytes: b-lymphocytes form antibodies t-lymphocytes fight viruses and tumour cells, graft rejection and stimulate b cells. David Pisani Renal Pathology Renal Failure- drop in eGFR 1. Pre renal: occurs secondary to haemodynamic compromise ( cardiovascular function becomes unreliable) with renal hypoperfusion (not enough blood to the heart). 2. Renal: problems in nephron/ renal interstitium 3. Post-renal: problems in outflow tract Diseases of the Glomerulus (most immunologically mediated) Nephrotic syndrome: massive proteinuria (hypoalbuminemia- not enough albumin and oedema- build up of fluid) Nephritic syndrome: mild proteinuria (microscopic haematuria- blood in urine, hypertension, severe azotaemia- blood has a lot of nitrogen) Treatment ○ Withdrawal of offending agent- drugs ○ Treatment of underling cause- Hep B/C/ tumours ○ Immunosuppression ○ Renal support- dialysis/ transplantation Diseases of Renal Tubules and Interstitium Acute pyelonephritis: bacterial infection causing inflammation of kidneys. ○ Kidneys have yellow colour ○ Urine has pus in ureters and renal calyces ○ Treatment: Iv antibiotics Bacterial: arise on background of lower UTIs Acute TIN (drug induced) (acute renal failure) ○ Penicillin ○ NSAIDs ○ Diuretics Chronic TIN ○ Chronic obstructive pyelonephritis: local obstructive scarring secondary to repeated pyelonephritis ○ Reflux nephropathy: chronic reflux secondary to obstruction Vascular Diseases of the Kidney Thickening of renal microvasculature (injury of chronic hypertension) ○ The kidneys shrink and show cortical granularity (on the outside). This results in kidney failure. Malignant hypertension: fibrinoid necrosis (walls of blood vessels containing fibrin dies) ○ Kidneys become ischaemic and renal failure occurs Urinary Outflow obstruction Renal stones (cause haematuria- blood in urine and pyelonephritis) ○ Calcium oxalate: increase Ca in urine ○ Struvite (proteus infection cause by a bacteria) ○ Uric acid: increased acid In urine ○ Cystine: genetic defect in transporter Hydronephrosis (dilation of renal pelvis and calyces) ○ Congenital: urethral valves and abnormal renal anatomy ○ Foreign bodies: stones ○ Hyperplasia: benign prostatic hyperplasia ○ Inflammation: prostatitis (prostate infection), urethritis (tube that caries urine is swollen and sore), ureteritis (inflammation of ureter) Obstruction ○ Acute Bilateral Complete Obstruction: Typically obstruction of the urethra. Anuria with distended bladder. (no urine production) ○ Chronic Bilateral Obstruction: Typically prostatic hyperplasia. Markedly distended bladder, bilateral hydroureter/hydronephrosis. Paradoxical polyuria (urine output increases) ○ Acute Unilateral Complete Obstruction: Typically stone obstructing ureter. ○ Chronic Unilateral Obstruction: Typically strictures of the ureter. Hydroureter (ureter gets big) and hydronephrosis (dilation of renal collecting system). Often asymptomatic. Tumour of the kidney Renal cell carcinoma ○ Risks: smoking + hypertension ○ Clear cell RCC: renal mass with yellow- orange cut surface ○ May invade: renal vein and infiltrate to renal capsule Transitional cell carcinoma (in urinary bladder and renal pelvis) ○ Risks: cigarette smoking and occupational carcinogens, haematuria ○ Appears as papillary and solid tumours in pelvis and ureter Pathology of Lower Urinary Tract Disease of Urinary Bladder Most are bacterial and involve dysuria (pain in urethra) and pain and urinalysis (high WCC, positive nitrites, positive erythrocytes) and urine cultures. Treated with antibiotics  Urinary bladder malignancy ○ Transitional cell carcinomas ○ polypoid papillary lesions projecting from the mucosa of the bladder. Histologically low grade tumours (benign muscle lesion of bladder). ○ Ulceration and painless haematuria may occur ○ High grade lesions require chemotherapy Diseases of Prostate Benign Prostatic Hyperplasia ○ Affects transitional and central zones of prostate (inner) ○ Related to dihydrotestosterone levels ○ glandular hyperplasia (increased cell production) and stromal hypertrophy (cells enlarge) with nodular enlargement (enlargement of lymph nodes) of the prostate. ○ Obstruct outflow tract ○ Symptoms: hesitancy, poor urinary flow, post-micturition dribbling (involuntary loss of urine) and nocturia (get up at night to urinate), acute urinary retention and if neglected can cause chronic outflow obstruction. Prostatic Cancer ○ Caused by Androgens: dihydrotestosterone Genetics: BRCA1 Environmental: diet + industrial carcinogenesis ○ Occurs in: peripheral zone of the prostate (asymptomatic) and local ○ Detection: check up, protein specific antigen testing and MRI ○ Treatment: Androgen deprivation: chemical suppressants Radiotherapy: external beam radiotherapy Radical prostatectomy Prostatitis: Inflammation of the prostate ○ Acute prostatitis – infectious (similar to UTI) Symptoms: dysuria (pain of urethra), low back pain and pelvic pain Treatment: antibiotics ○ Chronic prostatitis- non infectious and asymptomatic Diseases of the testicle and epididymis Epididymo-orchitis: inflammation of epididymis/ testicle (infectious) ○ Neisseria gonorrhoea: transmitted via direct mucosal contact ○ Chlamydia trachomatis ○ Others: mycoplasma, ureaplasma ○ Childhood: mumps ○ Secondary to tuberculosis ○ Symptoms: swollen, painful epididymis/ testicle ○ Treatment: antibiotics Testicular torsion: twisting of the testicle around its cord ○ Results in ischemia and infarction of testis  ○ Treatment: surgery Testicular cancer ○ Metastasis occurs to para-aortic lymph nodes follċ1owed by liver and lung. ○ Treatment:: Orchidectomy Seminoma: radiotherapy + chemotherapy Non-seminoma: chemotherapy CNS- David Pisani General: Oxygen deprivation ○ Functional hypoxia: low po2 in blood ○ Ischaemia: tissue hypoperfusion, either due to hypotension or vascular obstruction Ischaemic stroke caused by: vascular occlusion Hemorrhagic stroke caused by: hemorrhagic conversion of an ischaemic stroke or rupture of a vessel Injury may be: ○ Global: affecting whole brain ○ Focal: affecting part of brain Ischaemic stroke: ○ Cessation of blood flow to a localised area ○ Causes: Atherosclerotic disease: plaque in brain Embolic disease: embolization of thrombi Vasculitis: inflammation of cerebral blood vessels ○ Symptoms: Facial drooping Slurring of speech Arm/ leg weakness Limited healing potential Hemorrhagic stroke ○ Caused by: intraparenchymal bleeding Hemorrhagic transformation of ischaemic stroke Hypertension Subarachnoid haemorrhage ○ Bleeding within the meninges where CSF flows (not inside the actual brain) ○ Symptoms: Blood under arterial pressure hence presents with thunderclap headache. Infectious disease: route of entry: Meningitis: inflammation of meninges (headache, rash, light bothers them) ○ Bacterial: most common ○ Viral: self limiting (HHV)  ○ Tb ○ Diagnosis: laminar puncture from spinal cord Encephalitis: inflammation of parenchyma ○ Bacterial: result in destructive intraparenchymal abscesses ○ Viruses: herpes ○ Fungal: in immunosuppressed ○ Protozoa: in immunosuppressed Entry: ○ Hematogenous: from blood (arterial/ venous) ○ Traumatic event ○ Local extension: extension from other sites (sepsis) ○ Peripheral nerves: with viruses (polio ex) Tumours In adults mainly in cerebellum Characteristics: ○ To classify them site & grade 14 Meningioma: tumours arising from the meninges, benign Gliomas: ○ Astrocytoma: highly aggressive ○ Oligodendroglioma: better prognosis ○ Ependymoma: central canal in spinal cord Metastatic lesions: Breast, lung tumours and melanoma are most likely the ones which metastasize to the brain. Neurodegenerative Parkinson’s: degeneration of substantia nigra hence, less coordination and tremor as they have inability to stop unwanted movements. Huntington’s disease: mutation in Huntington gene which develop global degeneration. (severe genetic anticipation) hence severe dementia, difficult emotions. Alzheimer’s: deposition of beta amyloid throughout the brain Multiple sclerosis: autoimmune disease (demyelinating) Daniel Farrugia Disorders of the Immune System Innate: cells which mediate an attack on foreign bodies Adaptive: responds to infection/ foreign antigen (b and t cells) MHC Classes 1 + 2= bind to different peptide fragments Central T cell Tolerance: apoptosis of autoreactive T cells Anergy: absence of the normal immune response to a particular antigen or allergen. Suppression: by T cells Activation: apoptosis Central B cell Tolerance (peripheral tolerance): allowed to modify Auto-reactive B cells which bind with strong affinity to self-antigens- are “deleted” hence receptor editing Peripheral: activated by T cells Immune tolerance: immune system does not respond to an antigen Hypersensitivity Reactions 1. antibodies: Anaphylaxis (asthma u martina) a. Immediate response: vasodilation + smooth muscle spasm b. Second late phase reaction: inflammation + tissue destruction (necrosis) 2. hapten elicit an immune response only when attached to a large carrier) a. Opsonization b. Inflammation c. Cytotoxicity d. Cellular dysfunction: myasthenia gravis 3. Antigen antibody complexes form in the circulation- deposition in blood vessels leading to complement activation and acute inflammation. a. Joints b. Kidneys c. Lupus 4. T cell mediated (BCG vaccine) a. Direct b. Delayed Clinical features Systemic: skin erythema, bronchoconstriction Localised: inhaled antigen (organ specific manifestation)