Long Answer Pathology PDF

**CNS ischemic response** -- early stages 1. Cranial insult causes -- hemorrhage and vasogenic oedema. 2. Increase in ICP causes -- compression of cerebral arteries. 3. Shift of CSF to spinal cavity -- Monroe-Kellie hypothesis (increase in one compartment = decrease in another compartment)...

**CNS ischemic response** -- early stages 1. Cranial insult causes -- hemorrhage and vasogenic oedema. 2. Increase in ICP causes -- compression of cerebral arteries. 3. Shift of CSF to spinal cavity -- Monroe-Kellie hypothesis (increase in one compartment = decrease in another compartment) 4. Decrease in O~2~ (hypoxia) and increase in CO~2~ (hypercarbia) causes -- vasodilation of BV entering the brain. CNS ischemic response -- late stages 1. SNS stimulates systemic vasoconstriction causes -- increase in systolic BP. 2. Baroreceptors in aortic arch stimulate PNS vagus nerve to decrease HR causes -- bradycardia. 3. Increase in ICP compresses brain stem causing -- irregular respirations. 4. Excitotoxity 5. Neuronal death Cushing's triad (increased systolic BP, Bradycardia, Irregular respirations) **RAAS --** Renin is an enzyme that is released from the juxtaglomerular cells of the Kidneys in response to decreasing blood pressure. This converts Angiotensinogen (a protein made by the liver) into Angiotensin-1. Then Angiotensin converting enzyme (ACE) (an enzyme mostly produced by endothelial cells of the lungs) converts this into Angiotensin-2.   This molecule has 4 actions:  1. It acts on the arterioles to cause vasoconstriction. 2. This molecule causes Aldosterone to be released from the Adrenal Cortex. This causes increased reabsorption of Sodium and water in the distal convoluted tubules of the Kidneys. 3. Stimulates the release of Antidiuretic hormone / Vasopressin from the posterior pituitary. This hormone is produced by the hypothalamus, and it is also stimulated by osmoreceptors in the hypothalamus sensing increased blood osmolarity. It causes vasoconstriction of blood vessels and increased water reabsorption from the collecting ducts of the kidneys. 4. It acts on the thirst centre in the hypothalamus to promote the increased consumption of fluid to increase blood volume. **Pulmonary embolism --** blood-borne (fat, thrombus, air, etc.) substance lodges in pulmonary artery branch obstructing BF to the lungs. Symptoms - Hypoxia - Dyspnea - Uni-lateral chest pain - Tachycardia (HR increases in attempt to dislodge clot) - Hypotension **Shock --** inadequate O~2~ delivery and consumption at a cellular level -- two types circulatory and distributive To avoid shock adequate ventilation, oxygenation and perfusion are required. Circulatory shock 1. Hypovolemic (bleeding -- internal and or external, dehydration, third space losses -- infection, inflammation, and burns) 2. Cardiogenic (decreased CO despite adequate BV) either intrinsic -- MI, Arrythmias' and valve problems or extrinsic -- tension pneumothorax and cardiac tamponade 3. Obstructive (mechanic obstruction of BF) -- pulmonary embolism, dissecting aortic aneurism, pneumo/hemothorax and tumor. Distributive shock 1. Neurogenic -- where there is increased parasympathetic stimulation and decreased sympathetic stimulation due to a CNS injury, hypoxia or medication 2. Anaphylactic - where an allergen causes a type-I hypersensitivity reaction through an IgE response leading to bronchoconstriction, airway oedema, vasodilation and increased blood vessel permeability 3. Septic shock -characterised by a systemic infection, where mediators are released causing endothelial damage, increased blood vessel permeability and organ dysfunction. **Anaphylaxis --** a severe type one hypersensitivity reaction involving two or more body systems e.g., cardiovascular, respiratory, integumentary etc. causes the release of inflammatory mediators (histamine) causing widespread vasodilation, decreases BP, bronchoconstriction. Adrenergic receptors -- - Alpha 1 (located on smooth muscle of BV) -- adrenaline binds to cause vasoconstriction increasing TPR) - Beta 2 (airway smooth muscle) -- stabilize mast cell stopping degranulation, releasing of inflammatory molecules and bronchodilation. - Beta 1 (SA/AV node, myocardium) -- increase HR (chronotropy), increase conductivity (dromotropy), increase stroke volume (inotropy) **Hemothorax (blood in the plural cavity -- space between the parietal pleura and visceral pleura) vs pneumothorax (air in the plural cavity)** - Hemothorax -- can cause hypovolemic shock, obstructive shock, and lung collapse. - Pneumothorax -- increasing pressure causes lung to collapse (tension pneumothorax- air enters the plural space on inhalation via a defect in the chest wall/lung but does not exist during exhalation -- one way valve effect -- increasing pressure causes the mediastinum to shift the opposite side of the chest (mediastinal shift) **Cardiogenic pulmonary oedema --** fluid accumulation in the alveoli of the lungs due to left sided heart failure. - Left side of the heart takes blood from pulmonary circulation to systemic circulation, left sided heart failure (either systolic -- MI, or diastolic -- cardiac hypertrophy) causes an increased pressure in pulmonary circulation. - The mitral valve connects the left atrium and the left ventricle. The aortic valve separates the left ventricle and the aorta. If there is regurgitation, the valves don\'t close properly, and blood is allowed to flow backwards. If there is stenosis the valves don\'t open fully and less blood is able to leave the left side of the heart. Both of these situations could cause back log of blood in the pulmonary circulation. - Increased hydrostatic pressure in the pulmonary circulation leads to fluid entering the alveoli this pulmonary oedema will decrease ventilation and make it harder for gasses to diffuse in and out of the alveoli. - Acute treatment includes PEEP (positive end-expiratory pressure) to increase the pressure in the alveoli and vasodilators to decrease the hydrostatic pressure inside the capillaries surrounding the alveoli. - Decreased ventilation of alveoli can cause hypoxia. - To prevent V/Q mismatch body causes vasoconstriction of blood vessels in the surrounding area -- if widespread causes increased resistance to blood flow -- causing pulmonary hypertension and increased afterload in the right side of the heart. - Right side of heart must work harder to overcome resistance over time causing the right ventricle to undergo hypertrophy creating a smaller compartment for blood decreasing preload (diastolic heart failure) - Insufficient cardiac output from right ventricle causes backlog of blood in the right ventricle, superior and inferior vena cava, and systemic circulation. - Clinical manifestations -- jugular vein distention, ascites, and peripheral oedema. The 3 ways the Renin -- Angiotensin Aldosterone System (RAAS) is stimulated are 1. Decreased renal perfusion pressure, 2. Decreased BP causing sympathetic nerves to stimulate the Juxtaglomerular cells of the kidney to release Renin 3. Decreased solute concentration in distal convoluted tubules of the kidneys 1. It acts on the arterioles to cause VASOCONSTRICTION. 2. This molecule causes ALDOSTERONE to be released from the Adrenal cortex. This causes INCREASED reabsorption of SODIUM and H2O in the distal convoluted tubules of the KIDNEYS 3. Stimulates the release of ANTIDIURETIC HORMONE/VASOPRESSIN from the posterior pituitary. This hormone is produced by the hypothalamus and it is also stimulated by osmoreceptors in the hypothalamus sensing INCREASED BLOOD OSMOLARITY (less fluid more solute). It causes VASOCONSTRICTION of blood vessels and increased H2O reabsorption from the collecting ducts of the kidneys 4. It acts on the THIRST centre in the hypothalamus to promote the increased consumption of fluid to increase blood volume **Hypotension sympathetic response** -- - Stimulus occurs dropping BP. - Baroreceptors in aortic arch and carotid sinuses detect hypotension. - Decreased stimulation of these receptors stimulates cardioacceleratory center and vasomotor center in medulla of brain stem. - Sympathetic division of ANS is triggered. - Adrenaline and noradrenaline hormones/ neurotransmitters are released from sympathetic nerves and adrenal medulla. - Alpha-1 receptors on smooth muscle of arterioles and venules cause vasoconstriction to increase TPR (BP = CO x TPR) - Beta-1 receptors on SA and AV node increase HR (chronotropy) and increase electrical conduction speed (dromotropy) - Beta-1 receptors on myocardium increase contractility (inotropy) increasing BP as (BP = CO x TPR) AND (CO = HR x SV) Coronary artery disease -- disease of arteries that feed heart muscle (myocardium) - Coronary Artery Disease (CAD) or Coronary Heart Disease consists of chronic Ischaemic Heart Disease (IHD) and Acute Coronary Syndrome (ACS) - Ischaemic Heart Disease occurs when blood supply through the coronary arteries is insufficient for the demand of the myocardium (heart muscle). This could be due to narrowing of the coronary arteries due to atherosclerosis (Stable Angina) or vasospasm (Vasospastic Angina aka Prinzmetal Angina). - Silent Myocardial Ischaemia is a form of Ischaemic Heart Disease where there is ischaemia of the myocardium but the absence of the typical angina heart pain. This is a potential complication of nerve damage from poorly controlled Diabetes Mellitus known as autonomic neuropathy. - Acute Coronary Syndrome (ACS) occurs when the fibrous cap of an atherosclerotic plaque tears. This exposes the necrotic core (lipid core) which leads to a thrombus forming (clot). There are 3 forms of Acute Coronary Syndrome. Unstable Angina, NSTEMI and STEMI. The size of the thrombus and therefore how occluded the artery is determines whether the person will have Unstable Angina, NSTEMI or STEMI. **Hormonal regulation of blood glucose** -- Hyperglycemia -- occurs when BG levels to high which can lead to long term complications e.g., cardiovascular disease, neuropathy, and retinopathy. beta cells from the islets of Langerhans in the pancreas release insulin into the blood. Insulin facilitates the uptake of glucose by cells, especially in the liver, muscle, and adipose tissue reducing BG levels. Glycogenesis is the formation of glycogen from glucose that can be stored and lipogenesis conversion of glucose into fatty acids to be stored as triglycerides in adipose tissue. Hypoglycemia - when blood glucose levels are too low, leading to symptoms such as dizziness, confusion, and even loss of consciousness. Glucagon is released from the alpha cells from the the islets of Langerhans in the pancreas triggers glycogenesis -- breakdown of glycogen into glucose in the liver which enters the bloodstream raising BG levels. If there is not enough stored glucose gluconeogenesis will occur -- creation of glucose from non-carbohydrate sources e.g. amino acids and lipids stimulated by glucagon and cortisol. **Diabetes - type 1 VS type 2** -- Type 1 -- occurs due to a genetic predisposition activated when a triggering event occurs such as infection/trauma causing an autoimmune reaction -- body's immune system destroys insulin producing beta cells in the pancreas causing the body to produce little to no insulin thus patients require daily insulin treatment. Usually develops in childhood or adolescence but can occur at any age. Type 2 -- caused by insulin resistance in which body cell\'s do not respond correctly to insulin combined with a gradual decline in insulin production. Body still produces insulin, but it is inadequate, or body can't use it effectively (insulin resistance). Patients may need insulin therapy. **Diabetic ketoacidosis DKA** -- Diabetic ketoacidosis -If there is a lack of insulin, glucose cannot enter the cell - Gluconeogenesis is stimulated - Which is the creation of glucose from non-carbohydrate sources - Glycogenolysis -- breakdown of glycogen (stored glucose) also occurs - This increases blood glucose / hyperglycaemia - The breakdown of fat occurs (lipolysis) - However, fat burns in a carbohydrate flame so incomplete catabolism of fat occurs due to no glucose being able to enter the cell. - Therefore ketones are produced - Ketones are acidic therefore, metabolic acidosis occurs **Stroke --** A stroke is an impairment of cerebral circulation leading to damage to the brain There are 2 main types of stroke. Ischaemic and Haemorrhagic. Ischaemic strokes are due to an obstruction of blood flow. There are 2 main types. Thrombotic: This is due to an acute local thrombosis and complete occlusion at the site Embolic: an embolism travels from its origin to the brain, lodging in a smaller artery and preventing further blood flow Haemorrhagic strokes are due to a rupture of a cerebral blood vessel. The 2 main types are- Intracerebral haemorrhage: rupture of a cerebral blood vessel with haemorrhage into brain tissue itself. Subarachnoid haemorrhage: rupture of a cerebral blood vessel, with haemorrhage into the subarachnoid space **Asthma** is a chronic inflammatory disease of the airways characterised by: - Bronchoconstriction: Tightening of the muscles surrounding the airways. - Inflammation: Swelling and irritation of the airways / mucosal oedema. - Increased Mucus Production: Excess mucus clogging the airways. 1. Allergen Exposure: Individuals with asthma often have heightened sensitivity to allergens like pollen, dust mites, pet dander, or mould. 2. Immune Response: Upon exposure, the immune system overreacts, involving cells like mast cells, which release inflammatory mediators such as histamine, leukotrienes, and cytokines. 3. Bronchoconstriction: These mediators cause the smooth muscles around the airways to contract, leading to narrowing of the airways (bronchoconstriction). 4. Inflammation and Mucus Production: The mediators also cause inflammation and increased mucus production, further blocking the airways and making breathing difficult.