Human Path Sem 1

Atrophy: A decrease in cell size due to a reduced number and size of organelles and cytoskeletal structures. If enough cells are affected it can reduce tissue size. Common causes include reduced use, decreased hormonal stimulation, insufficient nutrients and denervation

Hypertrophy: A increase in cell size due to increased number and size of organelles and cytoskeletal structures. If enough cells are affceted it can increase tissue / organ size. Common causes include increased activity, load or hormonal stimulation

An increase in cell number which may lead to increased organ size if enough cells are affected. Typically occurs in tissue capable of mitotic division. Causes:
- Hormonal signalling (proliferation during menstrual cycle)
- Compensation (tissue regeneration and remodelling after injury)

Variability between the same mature cell type, this means variable cell and nucleus size / shape, thus differing mitotic rates.

Dysplasia is caused by a dysregulation of hormonal signals, chronic irritation / inflammation, viral infections and genetic mutations in cells.

Replacement of mature cell types done throuhg the reprogramming of undifferentiated stem cells in tissues. This differentiates into a different favoured cell type and is usually a short-term protective mechanism

This occurs inly in cells capable of mitotic division such as epithelia or glandular cells

It is caused by chronic irritation, destruction or damage

New growth or more simply a tumour. This can be benign or malignant. Benign is localised growth which is dangerous if it effects function of neighbouring tissues. Malignant is uncontrolled growth through tissue barriers into other tissues.

Variability between undifferentiated cells, this could be variable nucleues size and cell structure, increased mitotic abnormalaties and is often a charachteristic of cancer. Anaplasia is caused by cellular mutation.

Ischaemia: the reduced blood supply or consequently oxygen to tissue (hypoxia) which can be local or systemic leading to infarction (area of dead cells resulting from hypoxia)

Nutrient Imbalances: Calcium as an intracellular messenger. Increased Ca in cytoplasm activates damaging enzymes. Ultimately Insufficient diets or excessive diets can fatigue metabolic pathways and systems leading to dangerous metaboloties

Physical Factors: Temp extremes, trauma (mechanical), chemical

Apoptosis
- the programmed, controlled cell death with no inflammation. Can be beneficial or pathological eg; intracellular programs may trigger it when cell development is abnormal, cells are injured, aged or infected

Necrosis
- the premature, uncontrolled cell death, typically accompoanied with cell swelling or inflammation. Its always pathological and thus caused by factors external to the cell such as Ischaemia or infection

Coagulative – ischemia in solid organs whereby cell proteins are denatured

Liquefaction – brain infarction where dead cells liquify after lysis (cell death) due to enzyme activity

Caseous – form of coagulative necrosis whereby a cheesy substance forms. Common for tuberculosis

Fat – fatty acid deposits after fat cell lysis, eg; pancreatitis

Gangrenous – Gangrene is an area of necrotic tissue that has been invaded by bacteria. This will often occur in bowels or extremities where blood supply is deficient, but bacteria are present.

Pathogenicity – refers to the capacity of a microbe to cause disease: a feature of factors such as exotoxins, endotoxins and enzymes (ABILITY TO CAUSE DISEASE)

Virulence – degree to which a microorganism causes pathology; determined by specific pathogens and their invasive qualities, toxic qualities, adherence features and how well they avoid host defences. (DEGREE OF SEVERITY). Contributing structures include:
- Flagella which are thin rigid filaments of protein flagellin arranged as a hollow cylinder to enahce motility
- Pili which are hair like appendages required for bacterial mating and the transfer of genetic material. They can transfer antibiotic resistance
- Fimbriae which are also hair like appendages thinner than pili and much more numerous (thousands per cell). These are involved in the attachment of bacteria to host cells

1) Incubation – time between entry and clinical signs

2) Prodromal – signs vary between infections but its that typical feeling of fatigue, headache, appetite loss etc

3) Acute – clinical symptoms peak as infection is fully developed

4) Decline – Immune responses become effective

5) Convalescence – Recovery phase

Local includes: Inflammation, pain, tenderness, swelling, redness, warmth

Systemic includes: Fever, fatigue, weakness, headache, nausea (common to any signficiant infection

Chlamydiae
- these lack many enzymes required to grow and replicate in artificial media. There are obligate intracellular pathogens (meaning they must reside inside a living eukaryotic host cell to survive, metabolize, and replicate). Common for STIs / urogenital infections and respiratory infections

Rickettsiae
- Another obligate intracellular pathogen transmitted by insect vectors such as lice or ticks. Causes rocky mountain spotted fever

Cellulitis - causes red, swollen, painful, and warm skin, often on the lower legs. It occurs when bacteria enter through skin breaks like cuts, burns, or insect bites

Herpes simplex, often asymptomatic (spread through direct contact with lesion fluid or saliva). Causes recurring, painful, fluid-filled blisters or ulcers on the mouth or genitals

Tinea (ringworm) - spread via direct transmission (skin to skin or direct contact with contaminated object) it causes itchy, red, scaly, and sometimes ring-shaped rashes, commonly appearing on the feet (athlete's foot), groin (jock itch), or scalp.

1. Vasodilation
o ↑ blood flow
o Causes redness & heat
o Histamine and nitric oxide increased permeability by widening blood vessels  causes redness and heat

2. Increased permeability
o Endothelial gaps open
o Plasma proteins + leukocytes escape
o Accumulation of phagocytes and antimicrobial tissue in inflamed area

3. Exudate formation (collection of interstitial fluid)
o Fluid rich in proteins and immune cells, providing nutrients and moisture to wounds
o Exudate type differs according to trauma.
o Clearance of pathogens and accelerated tissue repair

Serous Exudate - watery, protein and WBC rich, common in allergic reactions or burns)

Fibrinous - thick and sticky exudate with high fibrin content indicating a more severe injury or infection

Purulent - greenish, yellow exudate with high WBC count common for bacterial infection)

Abscess - localised exudate formation such as around a tooth

Hemorrhagic - exudate cocnerned with blood vessel damage

Acute Inflammation
o Rapid Onset (minutes-hours)
o Short duration
o Dominated by neutrophils
o Usually beneficial and self-limiting
o Eg; Cut, infection or burn

Chronic Inflammation
o Long-term duration (weeks-years), occurs if the cause of inflammation is not eradictated
o Dominated by macrophages and lymphocytes
o Characterized by ongoing tissue destruction and repair
o Often pathological eg; atherosclerosis, tuberculosis

Local Inflammation
o Contained to one tissue
o Cardinal signs: Rubor (redness), Calor (warmth), Oedema (swelling), Dolor (pain) and function laesa (loss of function)

Systemic Inflammation
o Not confined to one tissue but rather body systems
o Fever
o Malaise (general feeling of unwell)
o Fatigue, Headache
o Anorexia (appetite loss)

The type of healing depends on the cause – say exposure to injurious agent is brief, the inflammation generally resolves itself with around 48 hours (eg; touching hot object). However we can split it into two main types:

1. Regeneration
• Replacement with identical tissue after minimal tissue damage
• Occurs in tissues with high mitotic capacity  Proliferation (epithelium, liver)

Advantages: full restoration
Disadvantages: limited to certain tissues

2. Repair/Replacement (Fibrosis/Scar Formation)
• Replacement with connective tissue (fibrotic tissue) after extensive damage in tissue without mitotic cells, thus tissue that cannot replace itself
• Associated with chronic inflammation
• Common in heart, brain

Advantages: structural integrity restored
Disadvantages: loss of function, scarring

1) Blood clot forms to seal the area

2) Migration of phagocytes to clean the area and rid it of foreign material

3) Granulation tissue will form and grow to fill the gap

4)New capillary-buds form which are highly vascular and fragile (gives red appearance)

5) Epithelial cells will grow and divide over the top of the wound

6) Fibroblasts enter the extracellular matrix to produce collagen fibres to strengthen the area

7) Fibroblasts and macrophages release growth factors (GFs) and cytokines to attract more fibroblasts and epithelial cells for proliferation and blood vessel formation (angiogenesis)

8) Cross-linking and shortening of collagen fibres to knit the wound together, strengthen it and create a scar (depending on damage extent)

9) The capillaries decrease, causinf the fading of redness

1st Degree
- Partial thickness which is superficial
- Appears red and painful but should heal readily without scarring eg; sunburn

2nd Degree
- Partial thickness which is deep
- Redness, oedema, blistering and pain throughout inflammatory stage
- Dead skin is sloughed off and healing occurs from proliferation of the cells at the edge of the blister

3rd and 4th Degree
- Full Thickness as area is coagulated or charred, meaning it is hard and dry on the surface
- The damaged tissue shrinks due to the pressure of the oedematous tissue beneath
- May be painless initially as nerves are destroyed, but very painful when inflammatory reaction occurs in adjacent tissue
- Requires skin grafts for healing as there are no cells available to replace lost cells

Recognition: The immune system detects foreign antigens (bacteria, viruses, toxins) using receptors on innate cells.

Activation and Mobilization: Innate cells release chemical signals (cytokines) that recruit more immune cells to the site of infection or injury.
Attack:

Innate Immunity: Phagocytes (macrophages, neutrophils) engulf pathogens, while the complement system destroys bacterial membranes.

Adaptive Immunity: Helper T cells coordinate the response, while Cytotoxic T cells kill infected cells and B cells produce antibodies to neutralize pathogens.

Regulation: Once the pathogen is cleared, the immune system shuts down the response to prevent tissue damage.

Memory: Specialized memory B and T cells remain, allowing for a faster, stronger response if the same pathogen reappears

- IgA: found in mucus, salvia, tears and breast milk
- IgD: Part of the B cell receptor which activates basophils and mast cells
- IgE: Protects against parasitic worms, responsible for allergic reactions
- IgG: Secreted by plasma cells in the blood and is able to cross the placenta into the fetus
- IgM: May be attached to the surfave of a B cell or secreted into the blood. Responsible for early stages of immunity

Hypersensitivity is the inappropriate (excessive and undesireable) immune response causing tissue damage. This can be split into four types.

Type I – Allergic Reactions
• IgE mediated
• Manifests in many forms – rash, fever, vomiting, anaphylaxis.
• Often allergic tendency is Inherited (atopic hypersensitivity), thus a response to a specific allergy (antigen)
• Mast cell degranulation
• Anaphylaxis, asthma

Type II – Cytotoxic
• Antibody-mediated cell destruction
• Circulating IgG or IgM antibodies mistakenly bind with antigen which activates phagocytosis
• Example when blood is receive from an incompatible donor: Type A recipient receives type B blood causing haemolysis as their respective antibodies bind to recipients/donors RBCs
• Autoimmune haemolytic anaemia

Type III – Immune Complex
• Antigen-antibody complexes deposit which activates complement, inducing tissue damage
• SLE (autoimmune disease where the immune system attacks healthy tissues, causing widespread inflammation)

Type IV – Delayed or Cell-mediated
• T cell mediated
• Contact dermatitis, TB skin test

When the immune system attacks self-antigens or its own body cells. Examples include;
- Rheumatoid Arthritis (RA): Affects joints, causing pain and inflammation.
- Systemic Lupus Erythematosus (Lupus): Can damage skin, joints, kidneys, and other organs.
- Type 1 Diabetes: Damages insulin-producing cells in the pancreas

In the case of a transplant rejection, foreign tissue is introduced in which the body's immune cells reject and thus attack in a Type IV hypersensitivity reaction.

This is the deficiency in one or multiple components of the immune system causing an inadequate immune response to antigens, increasing the risk of infection and cancer. Two types of immunodeficiency:

Primary – Basic developmental failure in immune system
- Think genetic

Secondary – Loss of immune response from a specific cause
- Infections (particularly viral like HIV)
- Malnutrition
- Cancer or chemoadiotherapy
- Age
- Stress

So AIDS is acquired immunodeficiency syndrome caused by the Human immunodeficiency Virus (HIV). HIV invades T-helper cells, replicates them and eventually destroys them causing a loss of defence against infection and cancer.

GH secretion is highest during childhood and so deficits lead to dwarfism unless corrected early.

Excess
• Gigantism (children – prior to epiphyseal closure)
• Acromegaly (adults – after epiphyseal plate closure. Growth of soft tissue and non-longitudinal bone growth)

Deficiency
• Growth failure / dwarfism (children)
• ↓ muscle mass, ↑ fat (adults)

Thyroid hormone disorders occur when the thyroid gland produces too much (hyperthyroidism) or too little (hypothyroidism) thyroid hormone, directly impacting metabolism, heart rate, and weight. Thyroid hormone disorders increase the base metabolic rate (BMR) of an individual

Hyperthyroidism
• ↑ metabolic rate
• Commonly autoimmune (graves disease)
• Weight loss, heat intolerance, tachycardia

Hypothyroidism
• ↓ metabolic rate
• Weight gain, cold intolerance, fatigue
• Commonly autoimmune or iodine deficiency

Glucocorticoids such as cortisol and cortisone are released in response to stress to increase blood glucose levels, suppress immune response and inhibit growth and repair. Adrenocorticotropic hormone is released to promote the release of glucocorticoids from the adrenal cortex

Cortisol Excess
• Cushing’s syndrome (Benign ACTH-secreting pituitary tumour)
• Muscle wasting, hyperglycaemia, hypertension
• Can be caused by LT or high dose anti-inflammatory steroid medication use, ACTH-secreting tumours of the pancreas, lung or thyroid and/or a Benign cortisol-secreting tumour of the adrenal cortex

Cortisol Deficiency
• Addison’s disease
• Where secretion of corticosteroids are low
• Hypotension, weight loss, fatigue. Patients require hormone replacement

Aldosterone increases the retention of sodium ions and a loss of potassium ions by the kidney. This retention of sodium ions leads to a retention of water. The release of aldosterone is stimulated by angiotensin II.

Excess Aldosterone
• Hyperaldosteronism
• Severe, often resistant high blood pressure, low potassium levels, and fluid retention
• It is primarily caused by benign adrenal tumours (Conns Syndrome) or bilateral adrenal hyperplasia
• Key symptoms include fatigue, headache, muscle cramps, and heart palpitations, with risks of stroke or kidney failure.

Blood dyscrasia is a general term for any disease or disorder of the blood, bone marrow, or lymphatic system, often involving abnormal cell counts (red cells, white cells, or platelets).

Myelodysplastic = general description for inadequate production of mature RBCs by bone marrow

Myeloproliferative = general description for overproduction of mature RBC’s by bone marrow

- Insufficient RBC’s and haemoglobin are known as anaemia.

- It can be due to abnormally low production of RBC’s/Hb, excessive loss or destruction of RBCs, just abnormal RBC's / Hb and Iron deficiency

- Too many RBCs is known as polycythaemia

- Erythropoiesis is dependant on iron, EPO, VB12 and folate: An insufficiency in any results in different classes of anaemia

Iron-Deficiency Anaemia
- Consequences of low O2 delivery to tissue includes: Fatigue, lethargy, pallor, delayed healing, Tachycardia and Dyspnea (breathlessness)

Pernicious Anaemia (second-most common)
- Caused by deficiency of Vitamin B12 or folate it produces much of the same symptoms as iron-deficient + swollen tongue, GI symptoms and neurological symptoms such as tingling and a loss of coordination

Sickle Cell Anaemia (Genetic disorder)
- Abnormal haemoglobin causes erythrocytes to form a sickle shape in low O2 conditions. The anaemia is due to haemolysis and occlusion of small vessels by sickle cells

Aplastic Anaemia
- Failure of the bone marrow to produce RBC’s due to a loss of stem cells. Its idiopathic (meaning unknown where it arises from).

Thalassemia (Most common genetic disorder)
- Faulty haemoglobin synthesis where there are abnormal or missing segments of normal haemoglobin. Therefore any of these RBC’s that are ‘abnormal’ are destroyed by the spleen prematurely and thus erythropoiesis cant keep up = decreased RBC availability

Leucopoenia
- Low number of WBC’s, usually due to neutropenia (the low number of neutrophils). Neutropenia is generally temporary and due to illness, infection cancers or drugs.
- This will increase susceptibility to infection (as neutrophils in the innate system are weakened)

Leukocytosis
- Abnormally high count of WBC usually indicating the body is fighting infection, inflammation, stress, or leukemia
- Neutrophilia or Eosinophilia

Blood Cancers: Leukoemia or Lymphoma (touched on later)
- Rapid, uncontrolled (malignant) production of abnormal, immature white blood cells in bone marrow

Thrombocytopaenia
- Low platelet numbers increasing bleeding risk and times. May be caused by autoimmune disorders, viral infection, spleen issues, cancers etc

Thrombocythemia
- High platelet numbers increasing thrombi formation and therefore the risk of thrombosis. This can be essential (myeloproliferative disorder) or reactive due to drugs used to treat thrombocytopaenia.
- Essential = body does it naturally, reactive = in response to something

Many proteins required for clotting or the formation of a thrombus are synthesized by the liver. Thus blood clotting fact disorders are generally the result of poor liver function causing defects in those clotting factors.

There can be Haemophilia or inherited disorders, Malabsorptive disorders such as Vitamin K deficiency, accidental in nature eg; ingestion of rat poison or proteins & lastly you can have a viral infection attacking these pathways such as ebola.

Haemophilia A
- Inherited blood clotting disorder driven by abnormal clotting factor VIII. It is an X-linked recessive trait, making it more common in males
- Symptoms = prolonged or severe haemorrhage after minor injury, spontaneous haemorrhage into joints causing pain and swelling and blood in urine and stool due to bleeding into kidneys and digestive tracts

Von Willebrand Disease
- Most common hereditary bleeding disorder caused by a deficiency or dysfunction of the von Willebrand factor (VWF), a protein essential for blood clotting and platelet adhesion.
- Symptoms are similar to Haemophilia but much milder, eg; rashes, nosebleeds, increased susceptibility to bleeding etc.

Infectious Mononucleosis (mono or glandular fever)
- Caused by Epstein-Barr Virus (herpes group)
- Transmission typically via saliva with an incubation period of 4-6 weeks.
- EBV penetrates pharyngeal and salivatory epithelial cells and spreads to lymphoid tissue to target B Cells.
- T cells are important in controlling the proliferation of infected cells
- Symptoms include: swollen lymph nodes due to proliferation of B cells and reactive T cells, sore throat, headache, fever, fatigue and just general infection

- Swollen tissues in extremities due to the blockage of lymphatic vessels causing lymph accumulation

- Treatment includes diuretics, rest, massage, elevation

Malignant neoplasms (cancers) involving lymphocyte proliferation in the lymph nodes. Two main disorders: Hodgkins and Non-Hodgkins. Unknown origin but it has higher rates in people who received radiation as a child.

- Hodgkins lymphoma is characteristic of defective B-Cells and reduced lymphocyte count with onset at 20-40 years of age. Prognosis is good if caught early but symptoms include: Large lymph node that is not painful, weight loss, fatigue, anaemia and loss of immune function. Treatment is radiation, chemotherapy, surgery

- Non-Hodgkins lymphoma is 90% more prevalent and is characteristic of defective B lymphocytes however some show up to affect T cells aswell. Its major differences from Hodgkins include: Multiple lymph nodes rather than a localised infection, widespread metastases, organ involvement and overall just more difficult to treat.

A neoplasm is an abnormal, excessive growth of tissue, commonly known as a tumor, resulting from cells dividing more than they should or not dying when they should. They are classified as benign (noncancerous) or malignant (cancerous).

The multi-step process by which normal cells are transformed into cancer cells through the accumulation of genetic mutations and epigenetic alterations. It involves uncontrolled cell division, evasion of cell death, and the development of tumors, usually driven by DNA damage from chemical, physical, or biological agents.

1. Initiation
• These cause the first mutation but does not result in an active cancer
• DNA damage/mutation
• Often irreversible
• Caused by carcinogens
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2. Promotion
• Cause further changes in DNA that affect cell division or differentiation.
• Proliferation of mutated cells
• Reversible
• Hormones, inflammation
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3. Progression
• Increased genetic instability
• Invasion and metastasis

Benign tumours tend to grow slowly and do not spread whereas malignant tumours can grow rapidly, invade and destroy nearby normal tissues.

Stage 1 – Cancer confined to organ of origin
Stage 2 – Cancer is locally invasive
Stage 3 – Cancer is spread to regional structures such as lymph nodes
Stage 4 – Cancer has metastasised (spread and formed new tumours in other parts of the body)

Cancers have different grades based on morphology of the cells involved:
Grade I = slow-growing, well differentiated appearing like original cells
Grade IV = fast-growing, show lots of anaplasias (loss of structure and function)

Structural abnormalities may be:
• Congenital (present at birth)
• Acquired (develop later due to disease)


Aetiological Factors
Congenital causes:
• Genetic mutations
• Chromosomal disorders (e.g. trisomies)
• Maternal infections (rubella – virus)
• Maternal diabetes
• Teratogens (alcohol, drugs)

Acquired causes:
• Rheumatic fever
• Ischaemic heart disease
• Hypertension
• Cardiomyopathies
• Degenerative valve disease
• Infective endocarditis

- Septal Defects
- Valvular Defects
- Cyanotic Defects

Ventricular septal defect (VSD) is the most common congenital heart defect making up 20-30% of congenital heart disorders. It is characterized by an opening in the intraventricular septum, where large openings permit a left-to-right shunt of blood.

Small defects are asymptomatic whereas large defects lead to:
◦ Pallor (decreased perfusion due to decreased CO)
◦ Tachycardia (sympathetic compensation for decreased CO)
◦ Sweating (increased SNS drive)
◦ Dyspnea on exertion (pulmonary edema)
◦ Increase risk of pneumonia (pulmonary edema)
◦ Intolerance for exercise (decreased CO, inefficient pump)
◦ Delayed growth and development (fatigue, poor feeding)

Valve Problems may be classified as either
a) Stenosis (narrowing of the valve, restricting the forward flow of blood)
b) Valvular incompetence (failure of a valve to close completely, flapping backwards)

Pulmonary Valve Stenosis

Aortic Valve Stenosis

Mitral Valve prolapse - floppy, balloon-like valve between LA and LV possibly causing regurgitation

Aortic Stenosis
- Congenital defect (aortic valve), age related calcification or rhematic heart disease
- One of the most common valve disorders (approx. 20% of older >65)
- Risk factors: Age, hypertension, high cholesterol, diabetes and chronic kidney disorders

Pulmonary Valve Stenosis
- Narrowing of the pulmonary valve, restricting blood flow from the right ventricle to pulmonary artery and lungs
- Causes symptoms like fatigue, chest pain and cyanosis.
- Often requires ballon valvuloplasty or surger

A congenital heart conditions where structural issues allow deoxygenated (blue) blood to bypass the lungs and enter systemic circulation, causing low oxygen levels and a blue-ish skin tint (cyanosis).

Tetralogy of Fallot (TOF)
A rare heart congenital defect combining four anatomical defects – this results in low-oxygen blood flowing through the body
Four components:
• VSD
• Pulmonary stenosis
• RV hypertrophy
• Overriding aorta

Mechanism:
Right → left shunt → deoxygenated blood enters systemic circulation
Signs:
• Cyanosis (bluish skin)
• “Tet spells” (severe and sudden cyanosis)
• Squatting relieves symptoms (increases SVR)

The heart attempts to maintain cardiac output:
Ventricular hypertrophy
• Due to pressure overload (e.g. aortic stenosis)

Chamber dilation
• Due to volume overload (e.g. regurgitation)

Frank-Starling mechanism
• Increasing venous return which Increases preload → stronger contraction (initially)

Neurohormonal activation
• Sympathetic stimulation
• RAAS activation

A cardiac dysrhythmia (arrhythmia) is an abnormal heart rhythm where the heart beats too fast (tachycardia), too slow (bradycardia), or irregularly, resulting from faults in the heart’s electrical system. Arrythmias can be sinus node abnormalities, atrial and ventricular conduction abnormalities.

These are all SA node abnormalities:

Bradycardia (<60 beats / minute)
– regular but slow heartrate
– results from vagal nerve/PNS stimulation

Tachycardia (100-160 beats / minute)
– regular but rapid heartrate – Wide QRS
– normal response to SNS stimulation
– compensation for decreased blood volume

Sick sinus syndrome (HR irregularity)
– marked by altering bradycardia and tachycardia and often requires mechanical pacemaker
• Causes: damage to SA node from heart surgery, drugs, heart disease

Palpitations
– Subjective awareness of heart contractions
• ↑caffeine, smoking or ↑stress

Atrial flutter
– Atrial heart rate of 160 to 350beats/min. Rapid and organised flutter of the heart
• AV node delays conduction – ventricular rate is slower (2:1 ratio)
• ↓stroke volume
• 'Saw-tooth' ECG
•Causes: Coronary heart disease, heart failure, mitral valve disease


Atrial fibrillation
- No distinct P waves
- Irregularly irregular rhythm
- leads to pooling of blood in the atria increasing thrombus risk
• Causes: Coronary heart disease, heart failure, mitral valve disease, hypertension, congenital heart defect

Ventricular tachycardia
• Normal contractions but very fast
• Wide QRS
• Rapid rate
Danger:
May deteriorate into ventricular fibrillation
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Ventricular fibrillation
• Chaotic waveform with very little or no contraction
• No cardiac output
• Cardiac arrest

A clinical syndrome in which the heart is unable to pump sufficient blood the metabolic needs of the body. When the heart cannot maintain pumping capability there are two main effects
- Cardiac Output decreases
- Back/Congestion develops as the output from the ventricle is less than the inflow of blood

Pump (muscle) can weaken/fail = cardiomyopathy
- Lack of fuel (ischemia)
- Muscle failure (infection)
- Overwork (hypertension --> Cardiac arrest)

Valvular disease and Arrhythmias

Smpathetic activation
• ↑ HR
• ↑ contractility
• Vasoconstriction (increases peripheral resistance)
• Implications: Increased HR decreases the efficiency of the heart, impeding filling and increasing workload. This will stress the ventricle walls leading to hypertrophy or increased myocardial blood/oxygen demand

RAAS activation
• Angiotensin II → vasoconstriction
• Aldosterone → Na⁺ retention to increase blood volume
• Implications: Vasoconstriction increases afterload and blood volume  Increases workload of the heart

ADH release
• Water retention
Initially helpful → chronically harmful

Frank-Starling Mechanism
• Increased venous return, stretching ventricular myocardium (increased preload) for a more forceful contraction and increased SV
• Good short-term mechanism but comes at a greater energy cost and increased metabolic demand

LEFT-SIDED CHF
Causes:
• Hypertension
• MI
• Aortic/mitral valve disease

Mechanism:
Blood backs up into lungs

Signs:
• Dyspnoea (shortness of breath)
• Orthopnoea (shortness of breath when lying supine)
• Pulmonary oedema (may lead to cyanosis)
• Crackles
• Pink frothy sputum

RIGHT-SIDED CHF
Causes:
• Left-sided failure (most common)
• Pulmonary hypertension
• Chronic lung disease

Mechanism:
Blood backs up into systemic circulation. NOTE: L and R sided failure commonly co-exist

Signs:
• Peripheral oedema
• Ascites (fluid accumulation in peritoneal cavity causing marked abdominal distension/swelling)
• Hepatomegaly (abnormal enlargement of liver)
• Raised JVP

Arteriosclerosis is the general term describing the thickening, hardening and loss elasticity of arterial wall. Key features include:
- Degenerative changes
- Narrowed Lumen
- Reduced Compliance
- Increased vascular resistance

Atherosclerosis is a specific type of arteriosclerosis characterised by the formation of atheromatous plaques (atheroma) in large and medium arteries. Plaque contains lipids (cholesterol), foam cells, smooth muscle cells, calcium, fibrin and necrotic debris. It is fundamentally a chronic inflammatory disease of the arterial intima initiated by endothelial injury.

1) Endothelial Injury
Damaged endothelium becomes permeable to LDL and attracts the migration of inflammatory cells and other nutrients

2) LDL Oxidation
LDL enters the tunica intima and media and becomes oxidised which makes it highly inflammatory

3) Monocyte Recruitment
Monocytes enter vessel wall and become macrophages, these ingest oxLDL to become foam cells. The accumulation of these forms fatty streaks

4) Smooth muscle proliferation
Smooth muscle cells migrate from media to proliferate, these produce collage and a fibrous cap to form the final product mature atheromatous plaque

5) Plaque complications
Thrombus formations, progressive stenosis (narrowing of vessel), vessel wall weakening and a fibrous cap rupture which is the breakage of the thin, collagen-rich layer covering Atherosclerotic plaque to expose the necrotic core to blood  triggers thrombosis and therefore heart attacks and strokes etc.

Coronary Arteries
Stenosis:
• stable angina
• Reduced exercise tolerance
Plaque rupture:
• Thrombus
• Unstable angina
• Acute myocardial infarction (AMI)
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Cerebral Circulation
• Carotid plaque rupture → embolus → ischaemic stroke
• Transient ischaemic attack (TIA)
• Progressive stenosis → chronic cerebral hypoperfusion
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C) Peripheral Arteries (PVD)
Mechanism: Reduced arterial flow to legs
Clinical features:
• Intermittent claudication
• Cold limbs
• Weak pulses
• Ulcers
• Gangrene
Severe ischaemia → necrosis

The abnormal bulge, ballooning or weakening in the wall of the artery, Plaque weakens medial layer → vessel dilation.
Common sites:
• Abdominal aorta
• Thoracic aorta

Risk:
• Progressive dilation
• Thrombus formation
• Rupture → catastrophic haemorrhage

Hypertension is self-perpetuating, meaning:

Increased BP damages endothelial lining ➡️ Atherosclerosis ➡️ Reduced arterial compliance ➡️ Higher systolic pressure ➡️ Further endothelial damage

This cycle progressively worsens vascular disease

Deep Venous Thrombosis:
A thrombus formation in the vein caused by:
- Immobility
- Restrictive clothes
- Trauma, inflammation
- Increased blood coagulation

Varicose veins:
Weakness or defect in vein wall or valve, primarily superficial veins. These veins result in dilated superficial veins which may increase venous pooling

Persistent venous hypertension causes:
- Oedema buildup
- Hyperpigmentation
- Lipodermatosclerosis
- Venous ulcers

Cerebral Venous Sinus Thrombosis:
Rare but very serious location for a thrombosis as it blocks cerebral venous drainage ➡️ Increasing intracranial pressure.
- Presents with headaches

Coronary Artery Disease (CAD) is the impaired coronary blood flow and is the leading cause of death in the world. Atherosclerosis is the most common cause. CAD includes:
- Angina Pectoris
- Myocardial Infarction (MI) / Heart attack

Ischaemic Heart Disease (IHD) is myocardial dysfunction resulting from an imbalance between oxygen supply and oxygen demand.

In practice CAD describes the anatomical disease while IHD is the physiological consequence

Stage 1: Endothelial Dysfunction
Due to:
• Hypertension
• Smoking
• Diabetes
• Hyperlipidaemia

Results in:
• Increased LDL penetration
• Inflammation
• Plaque formation
→ Progressive coronary artery narrowing
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Stage 2: Fixed Stenosis
As plaque enlarges:
• Lumen narrows
• Coronary flow reserve decreases
At rest:
• Perfusion may be adequate
During exertion:
• Oxygen demand exceeds supply
• → Reversible ischaemia
This produces stable angina

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Stage 3: Plaque Rupture
Inflamed plaque:
• Fibrous cap weakens
• Ruptures
Platelets adhere → Thrombus formation

Two possibilities:
Partial occlusion (that is, restricted, not stopped blood flow)
→ Unstable angina pectoris

Complete occlusion:
→ Myocardial infarction
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Stage 4: Myocardial Infarction (MI)
Defined as: Prolonged ischemia leading to irreversible myocardial cell death

Shock is not a specific disease but a syndrome which occurs in many life-threatening conditions. In most cases, shock involves a low cardiac output and a decrease in circulating blood volume.

Hypovolaemic Shock – Loss of circulating blood volume
- Due to Hemorrhage, burns, sever dehydration, vomiting, diarrhoea
- ➡️ Decreased preload ➡️ Decreased SV ➡️ Decreased CO ➡️ Decreased BP

Cardiogenic Shock – Failure of left ventricle to maintain Cardiac output to circulation
- Due to MI, arrhythmias, congenital heart defects
- Key issue is the failure of the left ventricle to pump

Distributive (Vasogenic) Shock – loss of blood vessel tone (vasodilation)
- Severe vasodilation → ↓ peripheral resistance → blood pools in periphery → ↓ venous return → ↓ CO

- Volume is normal but the vascular space expands meaning the normal volume of blood does not fill the circulatory system

SUBTYPES OF SHOCK
Neurogenic Shock
• Loss of sympathetic tone
• Spinal cord injury
• Anaesthesia
• Severe brain injury
Results: Sympathetic activity decreases causing ↓ Peripheral resistance
Bradycardia possible
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Anaphylactic Shock
• Severe allergic reaction or immunologically mediated reaction
• Histamine release
Causes:
• Vasodilation
• Increased capillary permeability
• Bronchoconstriction
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Septic Shock
• Severe systemic infection
• Endotoxins (gram-negative bacteria) released from fungi or bacteria cause tissue damage
Mechanisms:
• Cytokine storm
• Inflammatory response= Vasodilation
• Capillary leak
• Microthrombi
• Often initially “warm shock” due to vasodilation

Sympathetic Nervous System Activation
Triggered by baroreceptors.

Effects:
• ↑ Heart rate
• ↑ Contractility
• Vasoconstriction
• Pallor
• Sweating and thirst
• Anxiety, restlessness
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2. RAAS Activation
↓ Renal perfusion → renin release
Angiotensin II:
• Vasoconstriction

Aldosterone:
• Na⁺ retention

ADH:
• Water retention
Goal:
Restore circulating volume.

STAGE 1: Initial or Compensated Shock
• Mild hypotension
• Tachycardia
• Cool skin
• Reduced urine output

Cellular oxygenation still marginally maintained.


STAGE 2: Progressive or Decompensated Shock
Tissue hypoxia develops causing cells to switch from aerobic metabolism to anaerobic metabolism. Without oxygen cells:

- ↓ ATP production
- Failure of Na⁺/K⁺ ATPase
- Cellular swelling
- Lactic acid accumulation
- Metabolic acidosis  worsens hypotension, causes vasodilation and depresses myocardial function

Step 1: Transmission
• Respiratory droplets
• Direct contact
• Fomites
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Step 2: Mucosal invasion
Viruses or bacteria:
• Attach to epithelial cells
• Invade mucosa
• Trigger innate immune response
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Step 3: Inflammatory response
• Vasodilation
• Increased capillary permeability
• Mucosal oedema
• Exudate formation
→ Nasal congestion
→ Rhinorrhoea
→ Sore throat
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Step 4: Impaired mucociliary clearance
Cilia damaged → mucus accumulates → secondary bacterial infection risk

Common Cold
• Rhinovirus, adenovirus, coronavirus
• Highly contagious and transmitted via nasal mucosal secretions
• Localised symptoms
• Risk of secondary bacterial infection
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Influenza
• Orthomyxovirus
• 1-4 day incubation period (although infectious prior to symptoms)
• More systemic
• Fever, myalgia, fatigue
• Higher pneumonia risk
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Croup (Laryngotracheobronchitis)
• Parainfluenza virus and adenoviruses
• Occurs in children between 1 and 2 years of age
• Airway/lumen narrowing
• Barking cough
• Inspiratory stridor (high-pitched breathing sound during inhalation)

Mechanism:
Upper respiratory viral invasion → mucosal inflammation, nasal congestion, exudate, cough → Swelling and inflammation

Sinusitis
• The inflammation of the mucous membranes in the sinus cavities, typically caused by viral infections like the cold, but also bacteria/allergies
• Mucosal obstruction → trapped secretions → bacterial growth
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Tonsillitis / Pharyngitis
• Streptococcus species
• Exudate formation
• Lymphoid hypertrophy
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Pertussis (Whooping Cough)
• Caused by Bordetella pertussis with transmission through airborne droplets
• Can be fatal in newborns aged <1yr
• Toxin damages ciliated epithelium
• Whooping cough sound on inspiration, apnoea, Impaired clearance, vomiting coughing

Step 1: Pathogen reaches alveoli
Via:
• Inhalation
• Aspiration
• Blood spread
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Step 2: Alveolar inflammation
• Macrophage activation
• Neutrophil recruitment
• Cytokine release
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Step 3: Exudate fills alveoli
• Protein-rich fluid
• RBCs
• Neutrophils
• Fibrin
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Step 4: Impaired gas exchange
• ↑ diffusion distance
• ↓ ventilation
• V/Q mismatch
→ Hypoxaemia
→ Dyspnoea
→ Cyanosis

The inflammation and congestion of lungs, causes include:

Bacterial:
• Streptococcus pneumoniae (lobar)
• Staphylococcus aureus
• Legionella

Viral:
• Influenza
• RSV
• Coronavirus

Fungal:
• Pneumocystis (immunocompromised)

Risk Factors:
• Elderly
• Smoking
• Chronic lung disease
• Immunosuppression

Tuberculosis is a bacterial LRTI that involves mycobacterium tuberculosis. Its resistant to drying and many disinfectants (so it survives for weeks). In tuberculosis the cell wall resists neutrophils

It spreads through the air when an infected person coughs or sneezes. Symptoms include persistent cough, chest pain, weight loss, and fever. TB is treated with a combination of antibiotics over several months

Step 1: Inhalation
Inhalation of oral droplets Bacilli reach alveoli.
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Step 2: Macrophage Engulfment
Macrophages ingest bacteria but cannot destroy them.
TB survives intracellularly.
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Step 3: Granuloma Formation
Immune system walls off infection:
• Macrophages
• Lymphocytes
• Fibroblasts

Forms:
Tubercle (granuloma)

A characteristic X-ray finding in primary pulmonary tuberculosis (TB), consisting of a Ghon focus (a small, often calcified lesion in the lung parenchyma) and associated inflamed or calcified hilar lymph nodes
Primary TB lesion:
• Peripheral lung granuloma
• Plus infected hilar lymph node

Together:
= Ghon complex

Aspiration

Obstructive Sleep Apnoea (OSA)

Cystic Fibrosis

Asthma

The entry of food, fluid, vomitus or foreign material into trachea and lungs, most often being the right lung causing choking, gagging and/or pneumonia.

Depending on the contents and location (i.e size, liquid form) it will inhibit gaseous exchange and diffusion.

Defined as the repeated collapse of pharyngeal airways during sleep causing airflow cessation > 10 seconds, more than 5 times/hour. Mechansim of disease
During sleep:
• Pharyngeal muscles relax
• Soft tissue collapses
• Airway obstructed

Pathophysiological Consequences
• Intermittent hypoxia
• Sympathetic activation
• Pulmonary vasoconstriction

Chronic:
• Pulmonary hypertension
• Right-sided heart failure (cor pulmonale)
• Fatigue and cognitive impairment

Inherited disorder (CFTR gene mutation) causing obstruction as there is defective chloride transport, causing thick, sticky mucus to form.

Pulmonary Effects
• Mucus plugs bronchioles
• Causing air trapping or Atelectasis (partial or complete collapse of alveoli)
• Permanent damage to bronchial walls as a result
Chronic inflammation → bronchiectasis → fibrosis → respiratory failure → Cor pulmonale (RHS CHF)

Hypersensitive or hyperresponsive airways. Two types:
• Extrinsic (IgE-mediated)
• Intrinsic (non-allergic triggers)

Acute Asthma to the bronchi and bronchioles causes 3 stages of change
• Inflammation of mucosa with oedema
• Secretion of thick mucus
• Bronchoconstriction

PHASE 1: Antigen reacts with IgE on previously sensitised mast cells in the respiratory mucosa causing the release of histamines, kinins and prostaglandins.
These cause inflammation, bronchospasms, oedema and increased mucus secretions

PHASE 2: Increased leukocytes (WBCs, particularly eosinophils) release chemical mediators resulting in prolonged inflammation, bronchoconstriction and epithelial damage

Partial obstruction:
• Air trapping
• Hyperinflation
• ↑ residual volume

Total obstruction:
• Mucus plugs
• Atelectasis

Chronic Obstructive Diseases (COPD)

Emphysema

Chronic Bronchitis

COPD Involves progressive and irreversible damage to lungs, this includes emphysema and chronic bronchitis. primarily caused by smoking—that restricts airflow, causing chronic cough, wheezing, and severe shortness of breath. It includes emphysema (damaged air sacs) and chronic bronchitis (inflamed airways), which worsen over time.

Destruction of alveolar walls and septage, resulting in large permanently inflated alveolar air spaces and a loss of elastin function in alveolar walls. Contributing factors include:
Smoking:
• ↑ neutrophils
• ↑ elastase
• ↓ alpha-1 antitrypsin function

Genetic:
• Deficiency of alpha-1 antitrypsin

Consequences
• Loss of surface area/alveolar wall for gas exchange
• Loss of elastic recoil
• Air trapping
• Fibrosis and thickening of bronchial walls, narrowing airways
• V/Q mismatch

It is marked as significant changes in the bronchi associated with irritation, causing hypersecretion of mucus, frequent infections and a productive cough ≥3 months/year for ≥2 years.

Mechanism
Chronic irritation (smoking):
• Mucosal inflammation
• Goblet cell hyperplasia
• ↑ mucus
• ↓ cilia

Consequences
• Airway narrowing
• Mucus pooling
• Recurrent infection
• Hypoxia

Chronic hypoxia:
• Cyanosis
• Pulmonary hypertension leads to CHF
• Right-sided heart failure

Pulmonary fibrosis is the scarring of lung tissue whereby normal tissue is replaced by fibrotic tissue. This is a key restrictive lung disorders
- This reduces lung compliance (stiff lungs), inhibiting oxygen diffusion
- It is often caused by autoimmune disorders, tuberculosis or asbestosis

Pulmonary Oedema

Pulmonary Embolism

Congestive heart failure
- Causes left ventricle and/or right Av valve dysfunction
- Blood backs up on the left side of the heart as it cannot be pumped effectively into the systemic circuit
- This increased pressure in pulmonary blood vessels then force fluids out into the alveoli where the fluid collects and pools

Blockage of pulmonary artery (often from DVT). In other words, when a blood clot gets stuck in an artery in the lung, blocking blood flow to part of the lung.

Effects
Small embolus:
• Local hypoxia
• Vasoconstriction

Large embolus:
• ↑ Pulmonary vascular resistance
• Acute right heart strain
• ↓ Cardiac output
• Shock
• Sudden death

Pleural Effusion

Atelectasis

Pneumothorax

Flail Chest

Pleural Effusion – the accumulation of excess fluid in the pleural space (between visceral and parietal pleura), leading to lung compression. Lung compression means decreased tidal volume, lung compliance and alveoli are not ventilated properly meaning gaseous exchange fails (hypoxaemia).

Fluid balance in the pleural space depends on BHP, oncotic pressure, capillary permeability and lymphatic drainage.

Atelectasis – the collapse of alveoli (they become airless) or entire lung segments.

1. Obstructive Atelectasis
Airway blocked by:
• Mucus plug
• Tumour
• Foreign body

Mechanism:
1. Air distal to obstruction gets absorbed into blood.
2. No new air replaces it.
3. Alveoli collapse.
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2. Compression Atelectasis
External pressure on lung from:
• Pleural effusion
• Tumour
• Pneumothorax (air in pleural cavity)

Increased pressure on lung means → decreased lung expansion and alveoli collapse

Air entering the pleural space. This breaks the negative pressure that the pleural space usually has that keeps the lungs expanded. Types of Pneumothoraxes:

A closed pneumothorax is a partial or complete lung collapse caused by air leaking into the pleural space from within the lung itself, while the chest wall remains intact. Unlike an open pneumothorax (sucking chest wound), the injury is internal, often caused by ruptured blebs, trauma (like fractured ribs), or underlying lung diseases like COPD.

A spontaneous pneumothorax (TYPE OF CLOSED) is a sudden lung collapse caused by air leaking into the space between the lung and chest wall without injury, often due to ruptured small air blisters (blebs). Often occurs in tall thin young males or emphysema patients.

Mechanism
Blebs rupture → air leaks into pleural cavity.
Loss of negative pressure → lung recoils inward.

An open pneumothorax, or "sucking chest wound” occurs when a penetrating chest injury (e.g., gunshot or stab wound) creates an opening in the chest wall, allowing air to enter the pleural space directly from the atmosphere, causing lung collapse.

Tension pneumothorax is the most dangerous form where a one-way valve effect occurs. Meaning air can enter pleural space during inspiration but cannot leave during expiration. This is a medical emergency as pressure builds rapidly.

Flail Chest occurs when multiple adjacent ribs fracture in multiple places, creating a free-floating chest segment. Usually due to severe trauma eg; car crashes
It results in paradoxical, abnormal breathing (segment moves in on inhalation, out on exhalation), intense pain, severe breathing difficulty, and hypoxemia, often requiring hospitalization for weeks to months

ARDS is severe inflammatory lung injury causing fluid buildup in alveoli, resulting in rapid and severe hypoxaemia (low blood O2), damage and respiratory failure. Common causes include:
- Severe infection
- Trauma
- Aspiration
- Pneumonia
- Pancreatis

Stage 1: Initial Injury
Trigger causes massive inflammatory response in lungs.
Inflammatory mediators:
• cytokines
• neutrophils
• proteases
These damage the alveolar-capillary membrane.
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Stage 2: Increased Capillary Permeability
Endothelial and epithelial cells become damaged.
Fluid leaks into:
• interstitial space
• alveoli
This creates non-cardiogenic pulmonary oedema.
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Stage 3: Surfactant Dysfunction
Damage to type II alveolar cells reduces surfactant production.
Without surfactant:
• surface tension increases
• alveoli collapse
This causes widespread atelectasis (collapse of lung alveoli)
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Stage 4: Diffuse Alveolar Damage
Protein-rich fluid + dead cells form hyaline membranes lining alveoli.
These membranes:
• thicken diffusion barrier
• impair gas exchange
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Stage 5: Severe Gas Exchange Failure
Because many alveoli are:
• filled with fluid
• collapsed
• poorly ventilated
The lungs develop severe V/Q mismatch and shunting.

Acute respiratory failure occurs when the respiratory system cannot maintain adequate oxygenation or carbon dioxide removal. Two major forms exist:

Type 1 Respiratory Failure (Hypoxaemic)
Low oxygen levels. PaO2 < 50mmHg (Severe hypoxaemia)
(Normal is 80-100mmHg)
Causes:
• pneumonia (lung infection causing alveoli to inflame and to fill with fluid)
• ARDS
• pulmonary oedema
• pulmonary embolism

Mechanism: impaired oxygen transfer.
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Type 2 Respiratory Failure (Hypercapnic)
Elevated CO₂ levels. PaCO2 > 50mmHg (Hypercapnia)
(Normal is 35-45mmHg)
Causes:
• COPD
• neuromuscular disease
• severe airway obstruction
• drug overdose

Mechanism: inadequate ventilation → CO₂ accumulates

Cleft Lip and Cleft Palate

Apthous Ulcer

Hepres (HSV)

Gingivitis

Periodontitis

- A congenital birth defect where the roof of the mouth does not fuse properly during foetal development, creating an opening between the mouth and nasal cavity
- Cleft lip is a split or opening in one or both sides of the upper lip
- Cleft palate an opening in the roof of the mouth that may connect to the nose

- A painful, shallow whiterey mouth sores with red rims that usually heal on their own within 1–2 weeks. Causes are unknown but often linked to stress, mouth trauma, hormonal changes, and nutritional deficiencies (B12, iron).

- Infectious lifelong viral infection caused by the herpes simplex virus (HSV), mainly types HSV-1 (often oral) and HSV-2 (often genital)
- Close contact transmission, activated by stress, trauma and other infection.
- Formation of blisters, ulcers, clear fluid release (which contains HSV)

- Inflammation of gingiva (gums)

- Common, reversible, early-stage gum disease caused by plaque buildup, leading to tender, red, and bleeding gums. It is primarily caused by poor oral hygiene. It is treated through professional dental cleaning and improved home care, such as daily brushing and flossing.

- Periodontitis (gum disease) is a serious inflammatory infection caused by bacterial plaque buildup, leading to destroyed, receding gums and lost, loosened teeth

- Inflammation in tissuesone around tooth aggravated by smoking, cancer, diabetes and HIV

Hiatus Hernia
- The cardia of the stomach and the gastro-oesophageal junction slide above the diaphragm
- Weakness in the diaphragm muscle and increased abdominal pressure can cause this condition, including from obesity, persistent coughing, straining during bowel movements, or heavy lifting.
- Sliding hiatus is the most common type (90%)
- Rolling or paraesophageal hernia is where part of the fundus moves up through the an enlarged or weakened hiatus, causing food to lodge in pouch  Inflammation of mucus

Gastro-oesophageal reflux (GORD)
- a chronic condition where stomach acid frequently flows back into the food pipe, causing symptoms like heartburn, chest pain, and acid regurgitation. It is commonly caused by a weak lower oesophageal sphincter, hiatal hernia, or lifestyle factors like smoking and obesity

Acute Gastritis

Chronic Gastritis

Peptic Ulcers

Gastroenteritis

Dumping Syndrome

Pyloric Stenosis

Acute Gastritis
- Acute gastritis is a sudden, temporary inflammation of the stomach lining often caused by NSAID use, alcohol, infections, or severe stress.
- Appears as epigastric discomfort and pain/cramps, anorexia, nausea, vomiting etc

Chronic Gastritis
- Atrophy of mucosa and loss of secretory glands
- Decreased parietal cells  decreased Intrinsic Factor needed for B12 absorption (causes pernicious anemia)

Peptic Ulcers

- Single, small round cavities/sores in the stomach and proximal duodenum
- Commonly caused by bacteria eg; H. pylori or NSAIDS such as ibuprofen.
- Symptoms include a burning abdominal pain, bloating and nausea
- Typically accompanied by inflammation of the cavity leading to damage of mucosal barrier and increased acid-pepsin secretions

- Inflammation of the stomach and intestinal mucosa. Stomach  vomiting and intestine  Diarrhoea
- Usually due to infection (food or water-borne

- Rapid gastric emptying where food, particularly sugar moves too quickly from the stomach to the small intestine.
- Often caused by surgeries like gastric bypass or gastrectomy, it triggers abdominal cramps, nausea, diarrhea, dizziness, and rapid heartbeat.
- Symptoms occur shortly after meals (early) or 1–3 hours later (late). It is usually managed through dietary changes and often improves over time

- A condition in infants, usually aged 2–6 weeks, where the stomach outlet muscle thickens, blocking food from entering the small intestine. It causes persistent, projectile vomiting, hunger after feeding, and weight loss. Treatment is a curative surgical procedure called a pyloromyotomy, which cuts the thickened muscle
- This narrowing and obstruction of pyloric sphincter is developed or acquired
- Developmental: Hypertrophy of pyloric muscle, firm mass at pylorus or projectile vomiting immediately after feeding
- Acquired: Presence of fibrous scar tissue, persistent feeling of fullness, increased incidence of vomiting

Celiac Disease

Chronic Inflammatory bowel disease

Appendicitis

Diverticular Disease

Colorectal Cancer (CRC)

- a disease in which the small intestine is hypersensitive to gluten, leading to difficulty in digesting food. Its an inappropriate T-cell mediated immune response to alpha-gliadin (component of gluten), making it type IV hypersensitivity
- Abnormal response to gliadin  Atrophy of villi  Decreased surface area and enzyme production  malabsorption, muscle wasting and weight loss

- long-standing inflammation of the digestive tract, primarily consisting of Crohn's disease and ulcerative colitis.
- Crohn’s disease is the chronic, immune-mediated condition from anywhere in the GIT from mouth to anus, often affecting al layers and granulomas
- Crohn’s disease progression: Inflammation (skip lesions) --> Ulceration --> Coalesce (ulcers grow deep and linear, merging together with inflamed, non-ulcerated tissue to create a cobblestone appearance) --> Fissures/Abscesses/Fistula (form crevices/localised pockets of infection/abnormal tunnels between the bowel and organs or skin) --> Fibrosis --> Stricture and Obstruction (narrowed lumen = stricture)

- Ulcerative Colitis is inflammation of the mucosa and submucosa of the rectum and proximal colon only, causing a change in goblet cell activity, oedematous tissue and inner lining ulcerations. This causes fragile granulation tissue to form and an increased risk of colorectal cancer in the LT

- involves the formation of small, bulging pouches (diverticula) in the colonic wall, often causing cramping, abdominal pain (usually lower left), constipation, or diarrhea.
- It includes asymptomatic diverticulosis and inflamed diverticulitis.
- Causes include low-fiber diets, age, and high pressure in the bowel, while treatment ranges from high-fiber diets to antibiotics or surgery

- CRC or Bowel Cancer a common, often preventable, and treatable malignancy arising from polyps in the colon or rectum
- Key symptoms include persistent changes in bowel habits, blood in stool, unexplained weight loss, and abdominal pain.

Dysphagia (difficulty swallowing)
Mechanisms:
• oesophageal obstruction
• neuromuscular dysfunction
• inflammation
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Nausea and Vomiting
Caused by stimulation of the vomiting centre in the brainstem. A way of eliminating noxious substances
Triggers include:
• toxins
• infection
• gastric distension
• CNS signals
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Diarrhoea
Occurs when:
• intestinal secretion increases
• absorption decreases
• motility increases

Results in:
• fluid loss
• electrolyte imbalance
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Constipation
Mechanisms include:
• slow intestinal transit
• dehydration
• low fibre intake
• neurological dysfunction

Abdominal Pain
Caused by:
• inflammation
• obstruction
• ischemia
• distension of organ

Gallstones or Cholelithiasis are masses of solid material (calculi) that occur when bile components become imbalanced. This may consist of cholesterol or bile pigment (bilirubin) mixed with calcium salts etc.

Risk factors include:
• obesity
• female sex
• pregnancy
• high cholesterol diet
• rapid weight loss

When cholesterol concentration becomes too high:
1. cholesterol crystallises
2. crystals aggregate
3. stones form in gallbladder
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Manifestations
Small gallstones may be asymptomatic while large gallstones may block the cystic duct.

Hepatitis = inflammation of the liver.
________________________________________
Aetiology
Causes include:
• viral infection (hepatitis A, B, C)
• alcohol  fatty liver
• drugs
• autoimmune disease
________________________________________
Pathophysiology
Liver cells become damaged by:
• viral replication
• immune-mediated destruction
This leads to:
• hepatocyte injury
• impaired liver function
________________________________________
Manifestations
• fatigue
• jaundice
• dark urine
• hepatomegaly
• nausea

Preicteric Stage
- fatigue and malaise
- Anorexia and nausea
- General muscle wasting

Icteric Stage
- Onset of jaundice (yellowing of the skin and eyes caused by high bilirubin levels in the blood) due to biliary obstruction
- Stool light in colour, urine becomes darker
- Liver tender and enlarged with a mild aching pain

Posticteric Stage (recovery stage)
- Reductions in signs
- Weakness persists for weeks

Advanced, irreversible scarring (fibrosis) of the liver caused by chronic diseases like hepatitis, alcohol-associated liver disease, or fatty liver. It causes symptoms like fatigue, yellow skin (jaundice), swelling, and easy bruising, often remaining asymptomatic until severe.
- > 80% destruction leads to liver failure
Cirrhosis’ effects evolve from two factors
- Loss of hepatocyte function
- Interference with blood and bile flow in liver

Consequences
• impaired liver function
• portal hypertension
• reduced detoxification
• reduced protein synthesis

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Manifestations
• jaundice
• ascites
• spider angiomas
• hepatomegaly
• bleeding disorders
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Complications
• portal hypertension
• hepatic encephalopathy
• liver failure

Jaundice = yellow discolouration of skin and eyes due to elevated bilirubin.
________________________________________
A. Pre-hepatic Jaundice
Cause: excess breakdown of red blood cells.
Example: haemolytic anaemia.

Mechanism: too much bilirubin for liver to process.
________________________________________
B. (Intra) Hepatic Jaundice
Cause: liver disease.
Example: hepatitis or cirrhosis.

Mechanism: damaged hepatocytes cannot process bilirubin.
________________________________________
C. Post-hepatic (Obstructive) Jaundice
Cause: bile duct obstruction.
Examples:
• gallstones
• pancreatic cancer

Mechanism: bilirubin cannot reach intestines.

Normally pancreatic enzymes activate only in the intestine.
In pancreatitis:
1. pancreatic ducts become obstructed or damaged
2. digestive enzymes activate inside pancreas
3. pancreas begins digesting itself
This causes:
• inflammation
• tissue necrosis
• oedema
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Manifestations
• severe epigastric pain radiating to the back
• nausea and vomiting
• low-grade fever until infection develops
________________________________________
Complications
Severe pancreatitis may cause:
• pancreatic necrosis
• systemic inflammation
• shock (signs of shock are a symptom eg; cyanosis, rapid/weak pulse, tachycardia)
• multi-organ failure
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Aetiology
Most common causes:
• gallstones
• alcohol
• Triggered by conversion of trypsinogen to trypsin --> autodigestion of tissue

Diabetes mellitus is a metabolic disorder characterised by persistent hyperglycaemia due to impaired insulin secretion, insulin action, or both.
Insulin normally:
• promotes glucose uptake into muscle and fat
• stimulates glycogen storage in the liver
• inhibits fat and protein breakdown
When insulin is deficient or ineffective, glucose accumulates in the bloodstream.

Type 1 Diabetes Mellitus (T1DM)

Aetiology
Type 1 diabetes results from autoimmune destruction of pancreatic β-cells in the islets of Langerhans. The immune system attacks insulin-producing cells, leading to absolute insulin deficiency.

Risk Factors
• genetic predisposition (HLA genes)
• autoimmune diseases
• viral infections
• environmental triggers

Characteristics
• usually develops in childhood or adolescence
• rapid onset
• patients require lifelong insulin therapy

Type 2 Diabetes Mellitus (T2DM)

Aetiology
Type 2 diabetes results from insulin resistance combined with progressive β-cell dysfunction.
Insulin is present but body tissues respond poorly to it.

Major risk factors include:
• obesity (especially visceral fat)
• sedentary lifestyle
• genetic predisposition (markers and family history)
• Demographic (gender, age, ethnicity)
• increasing age
• metabolic syndrome
• hypertension
• dyslipidaemia

Characteristics
• most common form of diabetes
• typically develops gradually
• often associated with lifestyle factors

Polyuria (excessive urination), polydipsia (extreme thirst), and polyphagia (excessive hunger) are known as the "3 Ps" of diabetes mellitus

Initial Stage
When insulin is insufficient:
1. Glucose cannot enter cells efficiently
2. Blood glucose levels rise (hyperglycaemia)
3. Cells experience energy deprivation
Despite high blood glucose, tissues behave as though they are starving.
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Progressive Effects
Glycosuria
When blood glucose exceeds the renal threshold (~10 mmol/L):
• glucose spills into urine
• this is called glycosuria
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Polyuria
Glucose in urine draws water with it via osmotic diuresis, leading to:
• increased urine production
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Dehydration and Polydipsia
Loss of fluid causes:
• dehydration
• increased thirst (polydipsia)
________________________________________
Polyphagia
Because cells cannot use glucose effectively:
• the brain senses cellular starvation
• appetite increases
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Fat Breakdown
If glucose cannot be used for energy:
• the body breaks down fat (lipolysis)
• fatty acids are converted into ketone bodies
In Type 1 diabetes this can lead to diabetic ketoacidosis (DKA).

Hyperglycaemia damages endothelial cells (such as the layer in blood vessels and nerves). These complications are classified as either microvascular or macrovascular:

Microvascular Complications – damage to small blood vessels
- Eye: Retinopathy (damage to retinal blood vessels leading to microaneurysms, haemorrhaging and/or vision loss
- Kidney: Nephropathy (damage to kidney glomeruli leading to proteinuria (the presence of excess protein (typically albumin) in the urine, exceeding 150 mg/day) and/or possible chronic renal failure
- Diabetic Neuropathy: Nerve damage due to reduced blood supply and metabolic injury, symptoms include; numbness, tingling, pain and loss of sensation in feet

Macrovascular Complications – damage to large blood vessels
- Heart: Myocardial Infacrtion,
- Brain: Cerebral Vascular accident eg; Ischaemic Stroke, TIA or haemorrhagic stroke
- Peripherally: PVD due to obstruction or decreased blood flow (ischaemia)

Chronic Hyperglycaemia accelerates atherosclerosis as persistent high glucose leads to:
• glycation of proteins
• oxidative stress
• endothelial dysfunction

Type 1 Diabetes Treatment:
Because insulin production is absent:
Insulin Therapy: Patients require lifelong insulin replacement.

Methods include:
• multiple daily injections
• insulin pumps
• β-cell transplantation
Insulin allows glucose to enter cells and normalises blood glucose levels.
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Type 2 Diabetes Treatment:
Management usually occurs in stages.
Lifestyle Modification
• weight loss
• healthy diet (limit sugar)
• increased physical activity

Exercise improves insulin sensitivity.

Hypoglycaemia occurs when blood glucose falls below normal levels, it’s most common in people receiving insulin or glucose-lowering medications.
Causes of Hypoglycaemia
• excessive insulin administration
• missed meals
• increased physical activity
• alcohol consumption
• certain medications
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Pathophysiology
The brain relies heavily on glucose for energy.
When blood glucose falls:
1. the body activates sympathetic nervous system responses
2. counter-regulatory hormones are released (glucagon, adrenaline)
These attempt to raise blood glucose.
________________________________________
Signs and Symptoms
Symptoms arise from both autonomic activation and brain glucose deprivation.
Autonomic Symptoms
• sweating
• tremor
• palpitations
• anxiety
• hunger
________________________________________
Neuroglycopenic Symptoms
Due to insufficient glucose in the brain:
• confusion
• dizziness
• blurred vision
• weakness
• seizures
• loss of consciousness
Severe hypoglycaemia is a medical emergency.

Skeletal muscle fibres contain:
• myofibrils
• contractile proteins actin and myosin

Muscle contraction occurs through the sliding filament mechanism, where actin and myosin slide past each other. Muscles attach to bones via tendons, enabling movement at joints.

Bone is constantly remodelled in response to mechanical stress and metabolic demands.
The process involves:
1. Bone resorption by osteoclasts
2. Bone formation by osteoblasts
This cycle maintains bone strength

1. Activation: Osteocytes detect micro-damage and recruit osteoclast precursors.
2. Resorption: Osteoclasts break down mineralized tissue, leaving a resorption lacuna.
3. Reversal: Osteoclasts disappear, and stromal cells prepare the surface for new bone.
4. Formation: Osteoblasts lay down new matrix (osteoid) which subsequently mineralizes.
5. Termination: The surface is covered, and new bone rests

Important hormones include:
• Parathyroid hormone (PTH) – increases bone resorption to raise blood calcium
• Calcitonin – reduces bone resorption
• Vitamin D – increases calcium absorption
• Oestrogen – inhibits bone breakdown
Loss of oestrogen after menopause increases osteoporosis risk

There are 4 stages
Stage 1 – Haematoma Formation
Immediately after fracture:
• blood vessels rupture
• a blood clot (haematoma) forms
This initiates inflammation and attracts healing cells.
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Stage 2 – Soft Callus Formation
Fibroblasts and chondroblasts produce:
• collagen
• cartilage
This forms a soft callus, stabilising the fracture.
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Stage 3 – Hard Callus Formation
The soft callus is replaced by woven bone, forming a hard callus.
Osteoblasts deposit new bone matrix.
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Stage 4 – Bone Remodelling
Over months to years:
• woven bone is replaced with lamellar bone
• bone returns to near-normal structure

Osteoporosis

Rickets

Osteomalacia

Paget's Disease

Osteoporosis occurs when: bone resorption exceeds bone formation, resulting in reduced bone mass and density. This is a metabolic bone disorder and the most common disease affecting bones.

Two types:
- Primary osteoporosis – idiopathic, postmenopausal or senile (old age)
- Secondary osteoporosis – arising from a specific primary condition eg; Cushing’s syndrome
Bone becomes porous and fragile.
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Predisposing Factors
• ageing (decreases osteoblastic activity)
• postmenopausal oestrogen loss
• inactivity
• low calcium intake
• smoking
• corticosteroid use
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Complications
• fragility fractures
• vertebral compression fractures
• hip fractures

Rickets is the softening and weakening of bones in children, usually due to extreme, prolonged vitamin D, calcium, or phosphate deficiency

Vitamin D deficiency leads to:
• reduced calcium absorption
• poor bone mineralisation
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Consequences
Bones become soft and weak, causing deformities such as:
• bowed legs
• skeletal growth abnormalities
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Osteomalacia is the adult equivalent of rickets.

Pathophysiology: Bone matrix forms normally but fails to mineralise properly.
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Symptoms
• bone pain
• muscle weakness
• increased fracture risk

Paget’s disease is a progressive bone disease of adults where excessive bone destruction takes place and is replaced with fibrous tissue/abnormal bone.

Sequence:
1. excessive osteoclast activity
2. excessive osteoblast activity
3. formation of structurally abnormal bone
The resulting bone is enlarged but weak. Primarily in long bones, vertebral, pelvis and skull
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Complications
• bone pain
• fractures
• deformities
• arthritis
• nerve compression

Muscular Dystrophy is a group of genetic disorders that manifest as degermation of skeletal muscles. DMD is a severe, rapidly progressing and fatal form caused by mutations in the gene encoding dystrophin – a protein that stabilises muscle cells by maintaining cell shape.

Without dystrophin:
1. muscle fibres become fragile
2. repeated muscle damage occurs
3. muscle tissue degenerates
4. muscle is replaced with fat and connective tissue
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Characteristics
• X-linked disorder
• primarily affects boys
• progressive muscle weakness
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Clinical Signs
• delayed motor development (mental retardation)
• muscle weakness in infancy
• Gower’s sign (using hands to stand)
• calf pseudohypertrophy
• Vertebral deformities

Progression may eventually lead to respiratory and cardiac failure before the age of 20.

Nephrons are the functional units of the kidney with each kidney containing 1-1.25 million nephrons – cortical and juxtamedullary. Each nephron is divided into renal corpuscle (for filtration) and renal tubule (reabsorption and secretion).


Types of nephrons:
• Cortical nephrons (85%) – mainly in cortex, short loops. Flow with efferent arterioles where reabsorbed and secreted material enter
• Juxtamedullary nephrons (15%) – long loops into medulla; key for urine concentration

Renal corpuscle (in cortex):
• Glomerulus (capillary tuft – fenestrated capillaries) receives blood from afferent arterioles + Bowman’s capsule.
• Site of filtration.

Renal tubule (extends into medulla):
• Proximal convoluted tubule (PCT) → reabsorption of most water, ions, glucose, amino acids.
• Loop of Henle → descending limb (water reabsorption), ascending limb (Na⁺/Cl⁻ reabsorption).
• Distal convoluted tubule (DCT) → fine-tuning of electrolytes, acid–base balance.
• Collecting duct → receives input from many nephrons; regulated water reabsorption (ADH sensitive).

Renal circulation is unique (two capillary beds in series):

1. Renal artery → segmental arteries → interlobar arteries → arcuate arteries → interlobular arteries.

2. Afferent arteriole → glomerulus (capillary #1, filtration).

3. Efferent arteriole → peritubular capillaries (cortical nephrons) OR vasa recta (juxtamedullary nephrons).

4. These capillaries → interlobular veins → arcuate veins → interlobar veins → renal vein → IVC.

Urinary tract infections occur when microorganisms invade the urinary tract and trigger inflammation. Most infections are caused by bacteria, particularly Escherichia coli from the gastrointestinal tract

1) Cystitis
2) Pyelonephritis

Inflammation of the bladder wall and urethra, usually caused by bacterial infection. The bladder wall becomes irritated and hyperactive, simultaneously reducing its capacity

Common causes include:
• bacterial infection (E. coli)
• urinary catheterisation
• sexual activity
• poor hygiene
• urinary retention

Women are more susceptible due to shorter urethra. Urinary infection typically occurs via ascending infection:
1. bacteria enter the urethra
2. bacteria multiply in the bladder
3. bladder mucosa becomes inflamed
Inflammation causes irritation and swelling of the bladder lining.

Symptoms
• Pain in pelvic area
• urinary frequency
• urinary urgency
• dysuria (painful urination)
• cloudy or foul-smelling urine

Infection and inflammation of the kidney tissue and renal pelvis, involving one or both kidneys. The infection extends from the ureter into kidney as purulent exudate fills pelvis and renal calyces, compressing the renal artery and vein  causing obstruction and hydronephrosis (dilated area filled with urning also causing obstruction and ultimately necrosis)

Symptoms
• flank pain
• fever
• chills
• nausea and vomiting
• urinary symptoms

Severe infection can cause renal scarring

- Glomerulonephritis / Acute Post-Streptococcal Glomerulonephritis (APSGN)

- Nephrosis / Nephrotic Syndrome

Inflammation of the glomeruli, APSGN occurs following infection with Group A Streptococcus (2-10 days after incubation)
- Primarily affects children aged 3-7, especially boys
- Type III hypersensitivity reaction causing an inflammatory response in the glomeruli of both kidneys.

Pathogenesis
The disease is caused by an immune reaction:
1. streptococcal infection occurs (usually throat or skin)
2. immune complexes form
3. these complexes deposit in the glomeruli
4. inflammation damages glomerular capillaries

Consequences
• reduced filtration
• leakage of proteins and blood cells into urine

Symptoms
• haematuria (blood in urine)
• proteinuria
• oedema
• hypertension
• reduced urine output

Urinary obstruction occurs when urine flow is blocked, leading to increased pressure in the urinary system. This partial or complete obstructions leads to dilation of the renal pelvis, causing hydronephrosis – the swelling of one or both kidneys as urine becomes trapped, due to kidney stones, enlarged prostate or pregnancy

Urolithiasis (Kidney Stones) – refers to formation of stones in the urinary tract.
Causes
Stones form when urine becomes supersaturated with minerals, such as:
• calcium oxalate
• uric acid
• cystine
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Pathophysiology
Crystals form in the urine and gradually enlarge into stones.
If a stone blocks the ureter:
• urine flow is obstructed
• pressure builds up in the kidney
• severe pain occurs (renal colic)

This causes hydronephrosis as the renal pelvis and calyces dilate due to urine accumulation

– the most common form of kidney cancer in adults, originating in the lining of the kidney's small tubes. The primary tumour arises from tubule epithelium in the renal cortex (more often).
- Occurs more frequently in men and smokers
- Asymptomatic in early stages
- Often metastasises to liver, lung, bone or CNS at time of diagnosis.

Symptoms often appear late and include blood in the urine, back/flank pain, and unexplained weight loss. Primary treatments include surgery (nephrectomy)

Often marked by painless blood in the urine, occurs when cells in the bladder lining grow uncontrollably, frequently linked to smoking, chemical exposure, recurrent infection and excessive intake of analgesics.
- Multiple tumours develop and tends to recur
- Tumour is invasive through wall to adjacent structures meaning it metastases to pelvic lymph nodes, liver and bone
- Diagnosed by urine cytology and biopsy
- Early signs include painless blood in the urine (haematuria), which may appear rusty or bright red, increased frequency or urgency of urination, burning sensation, and, less commonly, lower abdominal or back pain

- Nephrosclerosis
- Adult Polycystic Kidney Disease (ADPKD)

Nephrosclerosis refers to hardening and narrowing of renal blood vessels. Often caused by:
• chronic hypertension
• diabetes

Pathophysiology
Reduced blood supply causes:
• kidney ischemia (narrowing of blood vessel lumen = reduction of blood supply)
• Thickening and hardening of the walls of arterioles and small arteries
• progressive nephron damage / destruction of renal tissue
• reduced kidney function

A genetic disorder causing multiple fluid-filled cysts in the kidneys. Autosomal dominant gene on chromosome 16 with first manifestations usually around age 40 as multiple cysts develop in both kidneys, causing enlargement, compression and destruction of kidney tissue.

Pathogenesis
- Mutations cause abnormal cell growth in kidney tubules.
- Cysts enlarge and compress normal kidney tissue.
- This leads to progressive kidney failure.

Renal failure occurs when the kidneys lose their ability to adequately filter blood and maintain fluid and electrolyte balance.
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Aetiology
Common causes include:
• diabetes mellitus
• hypertension
• glomerulonephritis
• prolonged obstruction
• toxic drugs (nephrotoxins)
• severe infection (pyelonephritis)
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Waste Product Accumulation

Substances such as urea and creatinine accumulate in the blood, causing uraemia.
Symptoms include:
• nausea
• fatigue
• confusion
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Fluid Retention
Reduced urine output leads to fluid overload, causing:
• oedema
• pulmonary congestion
• hypertension
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Electrolyte Imbalance
Kidney failure may cause:
• hyperkalaemia (high potassium)
• metabolic acidosis
• calcium imbalance
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Hormonal Effects
Reduced erythropoietin production causes anaemia.

AKI is a sudden decline in kidney function which may result from:
• severe dehydration
• blood loss (circulatory shock or heart failure)
• infection
• toxic drugs (nephrotoxins)
• urinary obstruction (calculi, blood clots, tumours)
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Focal effects or local functional effects depend on the specific area of the CNS that is damaged. Typical effects include:
- Motor dysfunction
- Sensory deficits
- Language disorders (aphasia – inability to comprehend or express language and dysarthria – inability to clearly articulate words as muscles used in speech are impacted due to motor dysfunction)

General effects may be due to focal lesions etc but more commonly represent global brain dysfunction. This includes:
- Impaired cognition
- Drowsiness
- Generalised weakness

Intracranial pressure is a result of brain fluids, blood and CSF. These are not compressible and thus a normal pressure within the cranial cavity must be maintained. Increased ICP is generally due to haemorrhage, oedema (trauma/infection), tumour or excessive CSF (increased production or reduced drainage)

ICP --> Overcoming blood flow autoregulation --> Ischemia --> Infarction / Necrosis of brain tissue

Abscess
- This is a localised infection of the frontal or temporal lobes caused by Staphylococci, streptococci, pneumococci
- This is a result of direct spread of organism from ear, throat, sinus or a site of injury or surgery. It can also be haematogenous spread (via blood)
- Leads to necrosis and oedema which increases focal signs and ICP

Meningitis
- Viral organisms reach brain via the blood or spread from nearby tissue. This infection spreads rapidly through the meninges of the brain leading to:
- Increased ICP, severe headache, back pain, confusion, drowsiness

Encephalitis
- Infection of the parenchymal or connective tissue in the brain and spinal cord eg; herpes simplex
- This results in necrosis and inflammation development in brain tissue, meningitis
- Early signs are confusion, fever, seizure, lethargy, vomiting

TBI is classified by whether the skull is breached (open vs. closed) and by the location of the brain damage in relation to the impact (direct/coup vs. contrecoup). A coup-contrecoup injury often combines these, causing damage at the point of impact and on the opposite side.

Types of TBI include: intracranial haemorrhage include:
- Concussions
- Contusions (bruising)
- Intracranial Haemorrhage

The primary types of intracranial haemorrhage include:
Epidural Hematoma (Extradural): Bleeding between the skull and the dura mater, often resulting from traumatic arterial rupture, such as the middle meningeal artery.

Subdural Hematoma: Bleeding beneath the dura mater and above the arachnoid membrane, usually caused by damaged bridging veins.

Subarachnoid Hemorrhage: Bleeding into the space between the arachnoid mater and pia mater, commonly caused by a ruptured aneurysm.

Intraparenchymal (Intracerebral) Hemorrhage: Bleeding directly into the brain tissue (parenchyma), frequently caused by uncontrolled hypertension or hemorrhagic stroke.

Different levels of the spinal cord provide afferent and efferent innervation of different parts of the body, including muscles, organs and other tissue. Thus injuries at these different levels will have various effects. Different types of spinal cord in juries include:

Cervical Spine Injury – involve damage to the vertebrae, ligaments, or spinal cord in the neck (C1-C7), often caused by trauma like car accidents, falls, or diving. Symptoms include severe neck pain, numbness, weakness, or paralysis, with high-level injuries risking breathing difficulties. Immediate immobilization is critical

Dislocation – the displacement of vertebra which may crush or compress the spinal cord

Compression – injury to spinal cord and a critical condition caused by pressure on the spinal cord from injuries, tumors, infections, or herniated discs, often resulting from degenerative osteoarthritis in people over 50.

Spinal shock is the initial period after injury where all neurologic activity ceases below and slightly above the level of the injury.

Permanent effects will see reflex activity resuming below level of injury but their descending control is lost (hyperreflexia). No communication with higher levels or brain which means a loss of sensation and motor control

Autonomic dysreflexia (AD) is a a potentially life-threatening medical emergency causing a sudden, dangerous spike in blood pressure, usually in individuals with spinal cord injuries at or above T6. Triggered by noxious stimuli below the injury (commonly a full bladder), it requires immediate treatment to prevent stroke or death

An ischaemic stroke is a condition where blood flow to a part of the brain is reduced or blocked leading to tissue hypoxia and cell death (infarction). Causes of ischaemic events include:

Thrombosis
• clot forms in cerebral artery (often due to atherosclerosis)

Embolism
• clot travels from elsewhere (e.g., heart → brain)

Systemic hypoperfusion
• severe hypotension/shock reduces brain perfusion

Transduction: the noxious stimuli activates nociceptors – this involves chemical release (prostaglandins, bradykinin, histamine)

Transmission: Pain signals travel via:
Aδ fibre (myelinated)
- Conduction of 20m / s
- Responds to intense mechanical or mechanothermal stimuli

C fibre (unmyelinated)
- Conduction 2m / s
- Responds to thermal, mechanical and chemical, thus a polymodal nociceptor

Transmission
1. Nociceptors activated → first-order neuron (Aδ fibers = fast, sharp; C fibers = slow, burning pain).
2. Synapse in dorsal horn.
3. Second-order neuron decussates in spinal cord.
4. Ascends via spinothalamic tract (lateral = pain, temperature whilst anterior = crude touch and pressure) → thalamus → primary somatosensory cortex & limbic areas.

Nociceptive Pain
Caused by actual tissue damage.
Examples:
• fracture
• burn
• inflammation

Inflammatory Pain
Occurs due to inflammatory mediators sensitising nociceptors.
• prostaglandins lower pain threshold
• leads to hypersensitivity

Neuropathic Pain
Caused by nerve damage or dysfunction.
Features:
• burning
• tingling
• shooting pain
Examples:
• diabetic neuropathy
• nerve injury

Phantom Pain
Pain felt in an amputated limb.
Mechanism:
• brain still has representation of the limb
• abnormal nerve signalling

Referred Pain
Pain perceived in a different location from its source.
Example:
• heart attack → left arm pain
Occurs due to shared neural pathways.

Headache
Caused by:
• vascular changes (activation of trigeminal nociceptors within the meningeal vessels)
• muscle tension
• inflammation
Types include:
• tension headache
• migraine (neurovascular origin)

• Alzheimer's disease
• Parkinson's disease
• Huntington's disease

Cause: progressive neuronal loss and protein accumulation

Multiple sclerosis (MS) is a chronic, often disabling autoimmune disease of the central nervous system where the immune system attacks myelin, the protective sheath covering nerves. It causes inflammation and scarring (lesions), disrupting nerve impulses.

A progressive neurodegenerative disorder caused by the loss of dopamine-producing brain cells (substantia nigra), primarily affecting motor control, balance, and movement. Common symptoms include tremors, stiffness (rigidity), slow movement (bradykinesia), and walking difficulties, often appearing after age 60

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that destroys motor neurons in the brain and spinal cord, causing voluntary muscle control loss, paralysis, and respiratory failure.

The functional consequences of this include:
- Progressive muscle weakness
- Paralysis
- Preserved cognition
- UMN signs such as spasticity and LMN signs such as atrophy

Myasthenia gravis (MG) is a chronic autoimmune disorder where immune system antibodies disrupt the connection between nerves and muscles (NMJs), leading to fluctuating voluntary muscle weakness and rapid fatigue.

Symptoms often start with droopy eyelids (ptosis), double vision (diplopia), and difficulty swallowing or talking. While not curable, it is highly manageable with medications and treatments that provide a good prognosis for most.

Treatment
• acetylcholinesterase inhibitors
• immunosuppressants
• thymectomy (in some cases)

Dementia is the progressive decline in cognition that affects daily functioning. Its got multiple types including
- Alzheimer’s disease (progressive brain cell destruction)
- Vascular dementia (impaired blood flow to the brain)
- Lewy Body dementia (abnormal protein deposits in the brain)
- Frontotemporal dementia (affects personality and behaviour but is characterised by the degeneration of the frontal and temporal lobes)

Prevalence for the condition increases with age with 60-70% Alzheimer cases being older people.

A progressive, irreversible neurodegenerative disorder and the most common form of dementia, primarily affecting memory, thinking, and behavior. It is characterized by the buildup of amyloid plaques and tau tangles in the brain, causing neurons to die and the brain to shrink.. β-amyloid plaques which are involved in neural growth and repair and tau tangles which are neurofibrillary tangles made of microtubule associated protein, tau. This is a intracellular scaffold that facilitates transport from cell body to extremities

A chronic, severe brain disorder affecting roughly 1% of the population, characterized by distortions in thinking, perception, emotions, and behavior. Symptoms include hallucinations, delusions, and disorganized thinking, often developing in late teens to early 30s

Psychosis is a severe mental disorder whereby thoughts and emotions are so impaired that there is loss of contact with external reality. Schizophrenia may have many other effects on thinking, even when patients are not psychotic.

Schizophrenia associated with an excess of dopaminergic transmission, while Parkinson’s with a deficit
• Antipsychotic medications commonly have Parkinsonian (sometimes termed ‘extrapyramidal’) side effects – tremor, rigidity, bradykinesia on Schizo patients