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Questions and Answers
Vitamin K is recommended for newborns due to lack of gut bacteria.
True
Vitamin C has a maximum absorption capacity of 3 g/day.
False
Scurvy is a deficiency condition associated with Vitamin C.
True
Cobalamin absorption requires intrinsic factor.
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Sources of Vitamin C include potatoes and carrots.
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The RDA for vitamin D for the elderly is 5-15 μg/day.
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Vitamin E has a high degree of toxicity and can cause severe adverse effects at low doses.
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Vitamin K is primarily obtained from dairy products.
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A deficiency of vitamin D can lead to rickets in children.
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Osteomalacia occurs in adults due to a failure of bones to mineralize properly.
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Vitamin K plays a role in the synthesis of prothrombin, essential for blood clotting.
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Vitamin D can only be obtained from food sources.
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For vitamin E, its sources include nuts, soybeans, and vegetable oil.
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Vitamin B12 can only be obtained from animal sources such as liver, meat, and eggs.
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Intrinsic factor is a glycoprotein produced in the stomach that is essential for the absorption of Vitamin B12.
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The human body can store significant amounts of Vitamin B12, approximately 4-5 mg.
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A common deficiency of Vitamin B12 can lead to neurological effects, such as demyelination and nerve cell death.
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Dietary deficiency of Vitamin B12 is very common, especially among non-vegans.
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Vitamin A is primarily derived from plant sources such as liver and dairy.
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Beta carotene is a pro-vitamin A found in animal products.
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Vitamin A plays a role in vision as part of the protein rhodopsin.
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The absorption of fat-soluble vitamins requires bile salts.
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Vitamin E is a water-soluble vitamin.
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A deficiency in vitamin A can lead to night blindness.
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Retinol binding protein carries vitamin B in the blood.
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Chronic ingestion of large amounts of vitamin A can lead to liver damage.
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High doses of niacin are used at 100x RDA in treating type IIb hyperlipoproteinemia.
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The RDA for biotin is firmly established and set at 30 μg/day.
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Pellagra is a deficiency syndrome of niacin and tryptophan characterized by three D's.
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Foods such as maize are high in niacin and tryptophan.
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Vitamin B12 is produced exclusively by plants.
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Adequate intake of pantothenate (B5) is established at 4-5 mg/day.
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Folate deficiency can lead to macrocytic anemia, affecting DNA synthesis.
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All forms of vitamin B6 have the same RDA of 1-1.7 mg/day.
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Vitamin A is exclusively derived from plant sources such as beta carotene.
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Excessive intake of vitamin A can have teratogenic effects and cause liver damage.
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Vitamin K1 is primarily sourced from animal products.
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The absorption of fat-soluble vitamins does not require normal pancreatic function.
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Retinol binding protein is crucial for carrying vitamin A in the blood.
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Vitamin A is essential only for visual functions within the body.
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Vitamin E is classified as a fat-soluble vitamin.
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Vitamin D can exclusively be obtained from dietary sources without any need for sunlight.
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Vitamin C can significantly increase plasma levels beyond 500 mg/day.
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Scurvy is characterized by symptoms including fatigue and fragile blood vessels due to a deficiency in Vitamin C.
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Vitamin B6 requires specific transport proteins for its absorption in the intestine.
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Biotin absorption occurs entirely by facilitated diffusion.
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The synthesis of carnitine is one of the main roles of Vitamin C.
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Vitamin K is only obtained from animal sources.
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Vitamin E's primary role is as an antioxidant in cell membranes.
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Rickets and osteomalacia are both caused by a deficiency of vitamin C.
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The active form of vitamin D is synthesized in the skin during exposure to sunlight.
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Vitamin E has a high toxicity threshold, causing adverse effects at doses above 300 mg/day.
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An adequate intake of 60-120 μg/day for vitamin K has been established.
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Vitamin D deficiency is most common in summer months.
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Fat malabsorption syndromes can lead to rare dietary deficiencies of vitamin E.
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A deficiency in riboflavin can lead to angular stomatitis, glossitis, dermatitis, and conjunctivitis.
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The RDA for thiamine is higher for individuals consuming more than 2000 kcal compared to those with lower energy intake.
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Wet beriberi is characterized by neurological symptoms such as peripheral neuropathy.
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Wernicke-Korsakoff syndrome often occurs in individuals with poor nutrition and decreased uptake of thiamine.
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Niacin can be synthesized efficiently from tryptophan.
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Riboflavin is essential for the clarity of the lens in the eye, and its deficiency can lead to opacity of the lens.
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Cobalamin is identified as Vitamin B9.
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Thiamine's requirement for adults is set at 0.8 to 1.0 mg per 1000 kcal for those with low energy intake.
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Deficiency of Vitamin B6 is commonly associated with increased sensitivity to steroid hormones.
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High doses of niacin can be used at over 100 times the RDA for treating type IIb hyperlipoproteinemia.
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The only dietary source of Vitamin B12 is from plant-based foods.
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Avidin is a glycoprotein found in raw egg whites that can lead to biotin deficiency when consumed in excessive amounts.
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The recommended dietary allowance (RDA) for pantothenate is firmly established at 5 mg/day.
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Consumption of maize can lead to an increased risk of vitamin deficiencies, especially niacin and tryptophan.
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Folic acid acts primarily as a 1-carbon carrier in DNA synthesis and amino acid metabolism.
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Pellagra is characterized by four D's: dementia, dermatitis, diarrhea, and diabetes.
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Chronic inflammation is characterized by a prolonged duration and delayed response.
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Chronic inflammation is solely caused by immediate tissue damage without any recurring stimulus.
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Lymphocytes and macrophages are the primary cells involved in chronic inflammation.
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Autoimmune diseases are one of the causes of chronic inflammation.
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Chronic inflammation begins abruptly and is independent of acute inflammation.
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Macrophages are the main effector cells in acute inflammation.
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Dendritic cells derive from bone marrow progenitors and are professional antigen presenting cells.
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M1 and M2 macrophages refer to two different types of antibodies.
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Activated macrophages release inflammatory mediators that can cause tissue destruction.
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Fibrosis is a feature that indicates the presence of acute inflammation.
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Sarcoidosis is characterized by non caseating granulomas.
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Asteroid bodies are associated with tuberculosis.
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Fibrinous inflammation involves the accumulation of fluid and fibrin due to decreased vessel permeability.
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Purulent inflammation is associated with the proliferation of pus-forming organisms.
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Schaumann bodies are calcium oxalate crystals found in certain granulomatous conditions.
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Staphylococcus aureus produces coagulase to cleave fibrinogen into fibrin.
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Cellulitis is a localized infection that does not spread.
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A sinus refers to a tract lined by granulation tissue leading from a chronically inflamed cavity to a surface.
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An abscess is a localized collection of blood.
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Chronic ulcers are always associated with scarring at the base.
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T-lymphocytes mature in the bone marrow.
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Plasma cells are not involved in antibody production.
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Eosinophils are effective killers of parasites.
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Mast cells are derived from eosinophils.
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Granulomatous inflammation can respond to both infectious and non-infectious agents.
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Tuberculosis is classified as a Type IV hypersensitivity reaction.
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Foreign body reactions cannot trigger granulomatous inflammation.
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Langhans giant cells are formed by the fusion of macrophages.
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Chronic inflammation is characterized by a prolonged duration and a delayed response.
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Chronic inflammation is solely caused by indigestible materials that have been implanted in wounds.
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The primary cells involved in chronic inflammation are neutrophils and eosinophils.
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Chronic inflammation can occur without a preceding acute inflammatory phase.
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Autoimmune diseases can trigger chronic inflammation in the body.
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The main effector cells in chronic inflammation are neutrophils.
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Activated macrophages release inflammatory mediators such as toxic oxygen metabolites.
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Dendritic cells differentiate into larger macrophages once they settle in tissues.
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Macrophages are classified into M1 and M2 types based on their function.
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Fibrosis is a feature of acute inflammation.
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Sarcoidosis is characterized by caseating granulomas.
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Fibrinous inflammation can occur in the serosal linings of the pericardium, peritoneum and pleura.
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Asteroid bodies are a type of cellular structure observed in sarcoidosis.
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Schaumann bodies are unrelated to any form of inflammation.
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Suppurative inflammation is characterized by the presence of pus-forming organisms.
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T-lymphocytes release lymphokines to regulate macrophage activation and recruitment.
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Eosinophils are ineffective killers of parasites.
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Granulomatous inflammation is a specific form of acute inflammation characterized by a rapid response.
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Tuberculosis is classified as Type IV hypersensitivity.
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B-lymphocytes can differentiate to form either memory B cells or T-helper cells.
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Basophils are the most common leukocyte type found in the blood.
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Giant cells in granulomatous inflammation are formed by the fusion of macrophages.
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Langerhans cells are primarily involved in the production of T-lymphocytes.
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Staphylococcus aureus lacks coagulase, which is essential for trapping bacteria and neutrophils.
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An abscess is described as a localized collection of dead and degenerate leucocytes.
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Acute ulcers always lead to deep penetrating tissue loss and scarring.
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A sinus is a tract lined by granulation tissue that connects an inflamed cavity to the surface.
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Fistulas are characterized by being open at only one end, restricting communication between surfaces.
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Chronic inflammation is characterized by a rapid onset and short duration.
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Lymphocytes and macrophages are the primary cells involved in chronic inflammation.
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Pneumoconiosis is a condition that can trigger chronic inflammation due to prolonged exposure to toxic agents.
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Chronic inflammation always occurs after an episode of acute inflammation.
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Autoimmune diseases such as rheumatoid arthritis do not contribute to chronic inflammation.
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Macrophages are activated by cytokines and bacterial ____.
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Dendritic cells differentiate into larger multinuclated giant cells in the tissues.
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M1 macrophages are primarily responsible for promoting tissue _____ and angiogenesis.
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Fibrosis is one of the key features distinguishing acute inflammation from chronic _____ disease.
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Activated macrophages release inflammatory mediators that are solely responsible for _____ cell death.
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Schaumann bodies are concentric calcifications found in non caseating granulomas associated with sarcoidosis.
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Type IV delayed hypersensitivity involves interactions primarily between B cells and neutrophils.
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Fibrinous inflammation is characterized by the accumulation of thin fluid derived from blood serum.
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The presence of purulent inflammation often suggests the proliferation of pus-forming organisms like Staphylococcus aureus.
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Cellulitis is a localized type of bacterial infection that typically occurs without any prior skin trauma.
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Skin blisters resulting from serous inflammation can occur due to factors such as viral infections and burns.
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An abscess primarily contains living neutrophils and healthy host tissue.
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Chronic ulcers are always associated with scarring at the base of the ulcer.
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A fistula is a tract that is closed at both ends, preventing any flow between two surfaces.
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A sinus leads from a chronically inflamed cavity to a surface but is not necessarily lined by granulation tissue.
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T-lymphocytes and B-lymphocytes are both produced in the thymus.
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Eosinophils are primarily known for their effectiveness against bacteria.
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Granulomatous inflammation is typically seen in response to easily digestible agents.
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Natural killer (NK) cells are classified as a type of B lymphocyte.
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Schistosomiasis can trigger granulomatous inflammation due to its parasitic nature.
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Caseating granulomas are a hallmark feature of tuberculosis.
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Basophils are the most abundant leukocyte in the bloodstream.
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Giant cells in granulomatous inflammation arise from the fusion of B-lymphocytes.
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Study Notes
Fat Soluble Vitamins
- Fat soluble vitamins include Vitamin A, Vitamin D, Vitamin E, and Vitamin K.
- Retinol is a vitamin A. Animal sources of retinol include liver, dairy, and egg yolk. Beta carotene is a pro-vitamin A, found in plants.
- Retinaldehyde is a light sensitive pigment in vision which binds to rhodopsin. Retinoic acid regulates gene expression.
- Vitamin A is carried in the blood by retinol binding protein, which is bound to transthyretin.
- Vitamin A deficiency can cause night blindness, xeropthalmia, and reproductive problems. Deficiency is often caused by protein malnutrition, which reduces retinol binding protein levels.
- Vitamin A is teratogenic (causes birth defects) in excess.
- Vitamin D is synthesized in the skin, but can be obtained from oily fish, eggs, and fortified foods.
- Vitamin D acts like a hormone, regulating calcium absorption and homeostasis. It has roles in immune function.
- Deficiency of Vitamin D causes rickets in children and osteomalacia in adults.
- Vitamin D is converted to its active form, calcitriol, by the liver and kidneys.
- Vitamin D toxicity can lead to high plasma calcium, causing blood vessel contraction and calcification of soft tissues.
- Vitamin E refers to a group of 8 tocopherols, which are antioxidants in cell membranes and help limit radical damage from polyunsaturated fatty acids.
- Vitamin E deficiency is rare but can occur in fat malabsorption syndromes, premature infants, and affect animals causing testicular atrophy, skeletal and cardiac muscle damage, and nervous system problems.
- Vitamin K is a cofactor for enzymes converting glutamate to γ-carboxyglutamate, essential for prothrombin production and factors II, VII, IX, X.
- Vitamin K is also found in osteocalcin, a protein in bone.
- Warfarin is a vitamin K antagonist and anticoagulant.
- Vitamin K is found in green leafy vegetables and is also synthesized by gut bacteria.
- Vitamin K deficiency causes coagulation defects, including increased prothrombin time.
- Vitamin K deficiency is most commonly caused by malabsorption in the gut, which can occur in conditions like celiac disease, Crohn’s disease, and fat malabsorption syndromes.
- Newborns receive a prophylactic injection of vitamin K due to lack of gut bacteria, poor milk content, and possible poor placental transfer.
Water Soluble Vitamins
- Water soluble vitamins include the Vitamin B complex and Vitamin C.
- Vitamin C (ascorbic acid) is a reducing agent and coenzyme in hydroxylation reactions, including the hydroxylation of proline and lysine for collagen synthesis.
- Vitamin C is also essential for carnitine synthesis.
- Vitamin C is absorbed by a specific transporter in the intestine, with a maximum absorption capacity of 1-2 g/day. Plasma levels do not increase significantly beyond 250 mg/day.
- Vitamin C promotes iron absorption in the intestine.
- Vitamin C deficiency causes scurvy which leads to sore gums, loose teeth, fragile blood vessels, anemia, fatigue, and defective connective tissue.
- Niacin (vitamin B3) is a coenzyme in energy metabolism and is essential for the synthesis of NAD+ and NADP+.
- Niacin deficiency symptoms include slow metabolism, decreased cold tolerance, and in severe cases, pellagra.
- Pellagra is a deficiency syndrome characterized by the three D’s: photosensitive dermatitis, diarrhea, and dementia.
- Maize is low in tryptophan and niacin, leading to niacin deficiency.
- Pantothenate (vitamin B5) is the functional moiety of coenzyme A and is essential for energy metabolism and fatty acid synthesis.
- Pantothenate deficiency is very rare due to its widespread availability in food.
- Pyridoxine (vitamin B6) includes pyridoxine, pyridoxamine, and pyridoxal.
- Pyridoxal phosphate, a derivative of pyridoxine, is a coenzyme for many enzymes, particularly those involved in amino acid metabolism.
- Pyridoxine deficiency is very rare but may lead to increased sensitivity to steroid hormones in animals. Some evidence suggests poor B6 intake is linked to poor breast cancer prognosis.
- Biotin (vitamin B7) is a coenzyme in carboxylation reactions, like those involving acetyl CoA carboxylase and pyruvate carboxylase.
- Biotin deficiency is rare but can cause dermatitis, alopecia, glossitis, nausea, and anorexia.
- Raw egg white contains avidin, a protein that binds biotin tightly, potentially causing deficiency when consumed in large amounts.
- Folic acid (vitamin B9) functions as a one-carbon carrier in the synthesis of amino acids, purines, and thymine.
- Folic acid is found in fruits, vegetables, and supplements.
- Folic acid deficiency causes megaloblastic (macrocytic) anemia. The lack of purine synthesis leads to abnormal development of blood cells, particularly in the bone marrow.
- Folic acid deficiency can also cause neural tube defects and low birth weight in pregnancy.
- Vitamin B12 (cobalamin) is produced only by bacteria/yeast. Animals receive Vitamin B12 from their gut flora or other animals through consumption of liver, meat, milk, and eggs.
- Vitamin B12 absorption requires intrinsic factor, a glycoprotein produced in the stomach.
- Vitamin B12 is stored in the body for several years.
- Vitamin B12 is a cofactor for leucine aminopeptidase, methylmalonyl-CoA mutase, and methionine synthase.
- Vitamin B12 deficiency causes megaloblastic anemia, similar to folic acid deficiency, and subacute combined degeneration of the spinal cord (neurological effects).
- Vitamin B12 deficiency can be caused by dietary deficiency, intestinal disease impairing absorption, bacterial overgrowth, and gastric malfunction that reduces intrinsic factor production.
Fat Soluble Vitamins
-
Vitamin A (Retinoids)
-
Dietary Sources:
- Animal: Retinyl esters (REs) in liver, dairy, egg yolk, fish oils
- Plant: Beta-carotene (pro-vitamin A)
-
Functions:
- Retinaldehyde is a light-sensitive pigment in vision, part of rhodopsin
- Retinoic acid regulates gene expression
- Absorption: Depends on normal pancreatic function, intestinal cells, and bile salts for lipid emulsification.
- Transport: Carried in blood bound to retinol-binding protein (RBP) which is itself bound to transthyretin.
-
Deficiency:
- Night blindness, xerophthalmia, reproductive problems (spermatogenesis, fetal resorption)
- Deficiency can result from protein malnutrition due to lack of RBP.
- Excess: Teratogenic, can cause liver and bone damage, alopecia, and headaches.
- RDA: 600-900 RAE (retinol activity equivalent) per day (1 µg retinol = 12 µg β-carotene).
-
Dietary Sources:
-
Vitamin D
- Functions: Hormone-like, regulates calcium absorption and homeostasis, involved in immune functions.
-
Deficiency:
- Rickets (children): failure of bones to mineralize properly
- Osteomalacia (adults): demineralization of bone.
- Sources: Few natural sources (oily fish, eggs, liver), fortified foods, synthesized in skin under sunlight.
- Conversion: Converted in the liver and kidney (with PTH) to the active form, calcitriol.
- Toxicity: Elevated plasma calcium, can cause blood vessel contraction, and soft tissue calcification.
- RDA: Varies based on skin synthesis, adequate intake for elderly: 5-15 µg/day.
-
Vitamin E
- Functions: Group of 8 tocopherols, primary antioxidant in cell membranes, limits radical damage from polyunsaturated fatty acid (PUFA) oxidation.
- Deficiency: Rare, can occur in fat malabsorption syndromes, premature infants (poor placental transfer).
- Deficiency Symptoms: Anemia, RBC membrane fragility, testicular atrophy, skeletal and cardiac muscle problems, nervous system problems.
- Sources: Nuts, soybeans, vegetable oils, spinach.
- Toxicity: Least toxic vitamin, 300 mg/day has no ill effects.
-
Vitamin K
- Functions: Cofactor for enzymes involved in carboxylation of glutamate to γ-carboxyglutamate. Essential for the formation of prothrombin, factors II, VII, IX, X, and other proteins like osteocalcin in bone.
- Sources: Green leafy vegetables, synthesized by gut bacteria.
-
Deficiency:
- Coagulation defects (increased prothrombin time)
- Osteoporosis (higher vitamin K correlates with greater bone density).
- Deficiency can be caused by poor gut absorption due to conditions like celiac disease, Crohn's disease, and fat malabsorption syndromes.
- Newborns receive a prophylactic injection of vitamin K due to lack of gut bacteria, poor milk content, and potential poor placental transfer.
- RDA: Not established, adequate intake: 60-120 µg/day.
Water Soluble Vitamins
-
Vitamin C (Ascorbic Acid)
- Functions: Main function is as a reducing agent, co-enzyme in hydroxylation reactions, particularly for proline and lysine in collagen synthesis, also involved in carnitine synthesis.
- Absorption: Absorbed by a specific transporter in the intestine, maximum capacity is 1-2 g/day, plasma levels don't increase significantly beyond 250 mg/day.
- Sources: Blackcurrants, guava, citrus fruits.
- Deficiency: Scurvy: Sore, spongy gums, loose teeth, fragile blood vessels, anemia, fatigue, defective connective tissue due to collagen problems.
- RDA: 45-90 mg/day.
Vitamin B Complex
-
Thiamine (B1)
- Functions: Co-enzyme for pyruvate dehydrogenase (glycolysis to Krebs cycle), α-ketoglutarate dehydrogenase (Krebs cycle), and transketolase (pentose phosphate pathway).
- Sources: Polished rice was linked to beri-beri, leading to its discovery.
- RDA: 0.8 - 1.0 mg for low energy intake, 0.5 mg/1000kcal for adults consuming more than 2000 kcal.
-
Deficiency: Beriberi
- Wet Symptoms: Cardiovascular involvement
- Dry Symptoms: Peripheral and central neuropathies
- Wernicke-Korsakoff Syndrome: Most common in alcoholics.
- Wernicke encephalopathy: Confusion, ataxia, paralysis of eye movement
- Korsakoff psychosis: Amnesia, confabulation.
-
Riboflavin (B2)
- Functions: Electron carriers in many redox reactions.
- Sources: Milk and dairy products, eggs, meat, fish.
- Deficiency: Angular stomatitis, glossitis, dermatitis, conjunctivitis, opacity of the lens (due to reduced glutathione reductase activity, impacting crystallin clarity).
- RDA: 0.9-1.3 mg/day.
-
Niacin (B3)
- Functions: Precursor for NAD and NADP, coenzymes in redox reactions and central roles in energy metabolism. Can be synthesized from tryptophan (inefficient process).
- Effects: Inhibits lipolysis in adipose tissue, reducing LDL and VLDL levels.
- Sources: Grains, milk, liver.
- RDA: 12-16 mg/day.
-
Deficiency: Pellagra:
- Dermatitis, Diarrhea, Dementia.
-
Pantothenate (B5)
- Functions: Functional moiety of coenzyme A, involved in energy metabolism, fatty acid synthesis.
- Sources: Widely available in diet, "from everywhere."
- Deficiency: Very rare.
- RDA: Not established, adequate intake: 4-5 mg/day.
-
Pyridoxine (B6)
- Functions: Includes pyridoxine, pyridoxamine, and pyridoxal. Pyridoxal phosphate is a coenzyme for many enzymes, particularly involved in amino acid metabolism (e.g., aminotransferases).
- Sources: Especially raw food (heating causes reaction with lysine).
- RDA: 1.0-1.7 mg/day.
- Deficiency: Rare, can lead to increased sensitivity to steroid hormones, some evidence links poor B6 intake to worse breast cancer prognosis.
-
Biotin (B7)
- Functions: Coenzyme in carboxylation reactions (e.g., acetyl-CoA carboxylase, pyruvate carboxylase).
- Sources: Widely available in diet, also produced by gut bacteria.
-
Deficiency: Rare, symptoms include dermatitis, alopecia, glossitis, nausea, anorexia.
- Raw egg white contains avidin, which tightly binds biotin and can cause deficiency if consumed in huge amounts (> 20/day).
- RDA: Not established, adequate intake: 20-30 µg/day.
-
Folic Acid (B9)
- Functions: Functions as a 1-carbon carrier involved in synthesis of amino acids, purines, and thymine.
- Sources: Fruits, vegetables, supplements.
- RDA: 300-400 µg/day.
- Deficiency: Macrocytic (megaloblastic) anemia due to purine deficiency affecting DNA synthesis, particularly noticeable in bone marrow. In pregnancy, deficiency can lead to neural tube defects (spina bifida) and low birth weight. Increase intake by 200-400 µg/day before conception.
-
Vitamin B12 (Cobalamin)
- Sources: Only produced by bacteria/yeast.
Chronic Inflammation
- Inflammation that persists for a prolonged period with a delayed response
- Results from a balance between ongoing tissue damage caused by a persistent stimulus and attempted eradication of the damaging agent followed by repair
- Characterized by the presence of lymphocytes and macrophages
- Usually begins insidiously
- Often preceded by acute inflammation
Chronic Inflammation Following Acute Inflammation
- Can occur from the progression of acute inflammation
- Examples: Progression of acute osteomyelitis to chronic osteomyelitis, a wood splinter implanted in a wound, surgical sutures
- Can also occur from recurrent episodes of acute inflammation
- Example: Chronic cholecystitis
Chronic Inflammation - Ab Initio
- Can occur from persistent infection
- Examples: Mycobacterium tuberculosis, Treponema pallidum, Fungi
- Can occur from prolonged exposure to toxic agents
- Examples: Pneumoconiosis (exposure to silica, asbestos, carbon dust)
Features of Chronic Inflammation
- Characterised by the presence of mononuclear cells (macrophages, lymphocytes, plasma cells) and fibrosis
Macrophages
- Main effector cells in chronic inflammation
- Monocytes extravasate (mediated by adhesion molecules and chemical mediators)
- Transform into larger macrophages
Role of Macrophages
- Activated by cytokines and bacterial endotoxins
- Phagocytosis
- Professional antigen presenting cells
- Release inflammatory mediators:
- Tissue destruction: Proteases, enzymes, AA metabolites, toxic oxygen metabolites, nitric oxide, coagulation factors, neutrophil chemotactic factors
- Vascular proliferation and fibrosis: Growth factors, cytokines, remodelling collagenase, metalloproteinase
Dendritic Cells
- Derive from bone marrow progenitors
- Circulate in blood as immature precursors and settle in tissues where they differentiate
- Professional antigen presenting cells; stimulate naïve T cells to initiate immune response
- Different types depending on location (e.g. Langerhans cells in the skin)
T-Lymphocytes
- Produced in bone marrow, mature in the thymus
- CD4 helper cells: Recognize MHC class II antigens
- CD8 cytotoxic cells: Recognize MHC class I antigens
- T cell activation requires binding of antigen/MHC complex
- Release lymphokines
- Regulate macrophage activation and recruitment via lymphokines
B-Lymphocytes
- Produced in bone marrow
- Differentiate into memory B cells or plasma cells
- Plasma cells are rich in rough endoplasmic reticulum and make antibodies
Natural Killer (NK) Cells
- Have a role in immunosurveillance and killing of infected or malignant cells
Mast Cells/Basophils
- Basophils are the least common leukocyte in the blood and migrate into tissues to become mast cells
Eosinophils
- Common in allergic inflammatory reactions
- Effective killers of parasites
- Phagocytic
- Major basic protein (MBP) toxic to parasites and contributes to tissue damage
- Mediate tissue damage
Granulomatous Inflammation
- Specific form of chronic inflammation
- Aggregation of macrophages with enlarged epithelium-like appearance surrounded by a rim of lymphocytes
- Giant cells: large cells with multiple nuclei
- Seen in response to persistent, poorly digestible agents that initiate a cell-mediated immune response (e.g. substances that resist lysosomal degradation, agents that induce T-cell hypersensitivity)
- Aims to control or remove the damaging agent
Granulomatous Inflammation - Causes
- Infection: Mycobacterium tuberculosis, Leprosy, Cat scratch disease, Syphilis, Histoplasmosis, Blastomycosis, Schistosomiasis, Leishmaniasis
- Foreign body: Exogenous (splinter, suture, graft material), Endogenous (keratin, hair shafts)
- Response to tumours
- Metal/dust: Berylliosis, Silicosis
- Unknown aetiology: Sarcoidosis, Crohn's disease
Tuberculosis
- Type IV hypersensitivity reaction
- Histological features: caseating granuloma, central necrosis, epithelioid macrophages and Langhans giant cells, T-helper cells, plasma cells, peripheral rim of suppressor T cells and fibroblasts
- Diagnostic tests: ZN stain, Culture, Fluorescent staining with auramine, PCR
Sarcoidosis
- Granulomatous condition of unknown aetiology
- Young adults, blacks > whites
- Affects any tissue
- Non-caseating 'naked' granuloma
- Schaumann bodies (concentric calcification) and asteroid bodies
Type IV Delayed Hypersensitivity
- Interaction between CD4 T helper cells and macrophages
- Macrophages present antigens via MHC II to CD4 helper cells causing their activation
- T cells produce cytokines (IL-2 and IFN-γ)
Morphological Patterns in Acute and Chronic Inflammation
- Serous inflammation: Accumulation of thin fluid derived from blood serum or secretion of fluid from mesothelial lining (effusion, skin blisters)
- Fibrinous inflammation: Accumulation of fluid and fibrin due to increased vessel permeability (seen on serosal linings)
- Suppurative inflammation: Localized proliferation of pus-forming organisms
- Ulcers: Local defect in epithelial surface produced by shedding of dead cells (skin and mucosal surfaces)
- Sinuses: Tract lined by granulation tissue leading from a chronically inflamed cavity to a surface
- Fistula: Track open at both ends creating abnormal communication between two surfaces
Chronic Inflammation
- A prolonged, delayed inflammatory response.
- Caused by a balance between ongoing tissue damage from a persistent stimulus and the body's attempts to eliminate it and repair the tissue.
- Typically involves lymphocytes and macrophages.
- Starts gradually and often follows acute inflammation.
Causes of Chronic Inflammation
- Persistent infection: Mycobacterium tuberculosis, Treponema pallidum, fungi.
- Prolonged exposure to toxic agents: Pneumoconiosis (e.g., silica, asbestos, carbon dust).
- Autoimmune diseases: Rheumatoid arthritis, Systemic Lupus Erythematosus (SLE).
- Diseases of unknown etiology: Inflammatory Bowel Disease.
Progression of Acute Inflammation
- Organization of an abscess: E.g., acute osteomyelitis progressing to chronic osteomyelitis.
- Presence of indigestible material: E.g., implanted wood, surgical sutures.
- Recurrent episodes of acute inflammation: E.g., chronic cholecystitis.
Microscopic Features of Chronic Inflammation
- Mononuclear Cells: Dominated by macrophages, lymphocytes, and plasma cells.
- Fibrosis: Scar tissue formation.
Macrophages
- Primary effector cells in chronic inflammation.
- Monocytes from the bloodstream undergo transformation into larger macrophages.
Macrophage Roles
- Activated by cytokines and bacterial endotoxins.
- Phagocytosis: Engulf and destroy foreign material.
- Professional Antigen Presenting Cells (APCs): Present antigens to lymphocytes to initiate immune responses.
-
Release inflammatory mediators:
- Tissue destruction: Proteases, enzymes, arachidonic acid metabolites, oxygen radicals, nitric oxide, coagulation factors, neutrophil chemotactic factors.
- Vascular proliferation (angiogenesis) and fibrosis: Growth factors, cytokines, collagenase, metalloproteinase.
Dendritic Cells
- Originate from bone marrow progenitors.
- Immature precursors circulate in blood: They differentiate into mature dendritic cells when they reach tissues.
- Professional APCs: Stimulate naive T cells to initiate the immune response.
- Different types exist, depending on their location. E.g., Langerhans cells in the skin.
T-Lymphocytes
- Produced in the bone marrow, mature in the thymus.
- T Cell Receptor (TCR) Rearrangement: Each T cell expresses a unique TCR that recognizes a specific antigen.
- CD4+ Helper Cells: Recognize antigens presented by MHC Class II molecules on APCs.
- CD8+ Cytotoxic Cells: Recognize antigens presented by MHC Class I molecules on infected cells.
- Activation: T cells are activated when their TCRs bind to an antigen/MHC complex.
- Lymphokine Production: Secrete cytokines that regulate immune responses.
T-Helper Cells
- TH1 Cells: Secrete IFN-γ, which activates macrophages and promotes a cell-mediated immune response.
- TH2 Cells: Secrete IL-4 and IL-5, which activate B cells to produce antibodies and promote a humoral immune response.
B-Lymphocytes
- Produced in the bone marrow.
- Differentiate into either memory B cells or plasma cells.
- Plasma Cells: Abundant in rough endoplasmic reticulum; produce antibodies (immunoglobulins).
Natural Killer (NK) Cells
- Innate Lymphoid Cells: Part of the innate immune system.
- Kill infected cells and tumor cells without prior sensitization. Recognize and eliminate cells that lack MHC Class I expression.
- Release cytotoxic granules: Contain perforin and granzyme, which induce apoptosis in target cells.
Mast Cells and Basophils
- Basophils are the least common leukocytes in the blood.
- Migratory: Basophils migrate into tissues and differentiate into mast cells.
- Degranulation: Release histamine, heparin, and other mediators in response to allergens or other stimuli.
- Allergic Reactions: Contribute to allergic inflammation.
Eosinophils
- Abundant in Allergic Reactions:
- Effective Against Parasites: Kill parasites by releasing toxic proteins.
- Phagocytosis: Engulf and destroy foreign material.
- Major Basic Protein (MBP): A toxic protein that destroys parasites and can contribute to tissue damage.
Granulomatous Inflammation
- A form of chronic inflammation characterized by the aggregation of macrophages.
- Epithelioid Macrophages: Macrophages with an enlarged, epithelium-like appearance.
- Giant Cells: Large cells with multiple nuclei formed from the fusion of macrophages.
- Rim of Lymphocytes: Surround the core of macrophages.
Granuloma Formation
- Caused by persistent, poorly digestible agents or those that induce a cell-mediated immune response.
- Aims: Control or eliminate the damaging agent.
Causes of Granulomatous Inflammation
- Infections: Mycobacterium tuberculosis, leprosy, cat scratch disease, syphilis, histoplasmosis, blastomycosis, schistosomiasis, toxoplasmosis, leishmaniasis.
-
Foreign Bodies:
- Exogenous: Splinters, sutures, graft materials.
- Endogenous: Keratin, hair shafts in pilonidal sinuses.
- Tumors: In response to certain tumors.
- Metal/Dust: Berylliosis, silicosis.
- Unknown Etiology: Sarcoidosis, Crohn's disease.
Tuberculosis
- Type IV hypersensitivity reaction (delayed-type hypersensitivity).
-
Histological Features: (lungs, lymph nodes)
- Caseating Granuloma: Central necrosis, surrounded by a ring of macrophages and lymphocytes.
- Epithelioid Macrophages and Langhans Giant Cells.
- T-Helper Cells: Within the granuloma.
- Plasma Cells: Occasionally present.
- Peripheral Rim of Suppressor T Cells and Fibroblasts.
- Diagnosis: ZN (Ziehl-Neelsen) stain, culture, fluorescent staining with auramine, PCR.
Sarcoidosis
- Granulomatous condition of unknown etiology.
- Commonly affects young adults, blacks > whites.
- Multi-systemic: Can affect any tissue.
- NON-caseating granuloma
- Schaumann Bodies: Concentric calcification (calcium oxalate crystals).
- Asteroid Bodies: Concentrically layered, spherical structures.
Type IV Delayed Hypersensitivity
- T cell-mediated immune response: Interaction between CD4+ helper T cells and macrophages.
- Mechanism: Macrophages present antigens to T cells via MHC Class II, triggering T cell activation.
- Cytokine Production: Activated T cells release IL-2 and IFN-γ, which amplify the immune response.
- Key Examples: Tuberculosis, fungal infections, sarcoidosis.
Morphologic Patterns in Inflammation
-
Serous Inflammation: Exudation of thin, watery fluid derived from serum or mesothelial cell secretions:
- Effusion: Accumulation of fluid in body cavities (peritoneum, pleura, pericardium).
- Skin Blisters: Caused by viral infections or burns.
-
Fibrinous Inflammation: Exudation of fibrinogen, which polymerizes into fibrin.
- Common sites: Serous linings of the pericardium, peritoneum and pleura.
- Resolution: May be removed by fibrinolysis.
-
Suppurative Inflammation (Purulent Inflammation): Characterized by the production of pus.
- Typical Organisms: Staphylococcus aureus, which produces coagulase, traps bacteria and neutrophils, localizing the infection.
- Cellulitis: Spreading bacterial infection of subcutaneous tissue.
-
Abscess: Localized collection of pus.
- Composition: Dead neutrophils, dead tissue cells, edema fluid, dead microorganisms.
-
Ulcers: Local defect in an epithelial surface caused by shedding of dead epithelial cells.
- Locations: Skin and mucosal surfaces (e.g., peptic ulcer).
-
Differentiation from erosions by extent of tissue loss:
- Acute Ulcers: Loss of full thickness of epithelium, may or may not have scarring at the base.
- Chronic Ulcers: Deep penetrating, always have scarring at the base.
-
Sinus: Tract lined by granulation tissue that connects a chronically inflamed cavity to a surface.
- Examples: Sinuses associated with osteomyelitis, pilonidal sinus.
-
Fistula: Abnormal communication between two surfaces, lined by granulation tissue, open at both ends.
- Example: Gastrointestinal fistula in Crohn's disease.
Chronic Inflammation
- Chronic inflammation is inflammation of a prolonged duration and delayed response.
- It results from a balance between progressive tissue damage caused by a persistent damaging stimulus and attempted eradication of the damaging agent followed by tissue repair.
- Chronic inflammatory cells are lymphocytes and macrophages.
- It begins insidiously.
- Preceded by acute inflammation.
Causes Of Chronic Inflammation
- Persistent infection.
- Prolonged exposure to toxic agents.
- Specific types of autoimmune diseases.
- Diseases of unknown aetiology.
Chronic Inflammation Following Acute Inflammation
- Progression of acute inflammation.
- Presence of indigestible material.
- Recurrent episodes of acute inflammation.
Features of Chronic Inflammation
- Mononuclear cells -macrophages, lymphocytes and plasma cells.
- Fibrosis
Macrophages
- The main effector cells in chronic inflammation.
- Extravasation of monocytes.
- Transformation into larger macrophages.
Role Of Macrophages
- Activated by cytokines and bacterial endotoxins.
- Phagocytosis.
- Are ‘professional’ antigen presenting cells.
- Release inflammatory mediators, causing tissue destruction, vascular proliferation (angiogenesis) and fibrosis.
M1 And M2 Macrophages
- Macrophages can be divided into two main subtypes:
- M1 macrophages: classically activated, pro-inflammatory, promote tissue destruction.
- M2 macrophages: alternatively activated, anti-inflammatory, promote tissue repair.
Dendritic Cells
- Dendritic cells derive from bone marrow progenitors.
- They are professional antigen presenting cells.
- They stimulate naive T cells to initiate an immune response.
T-Lymphocytes
- Produced in the bone marrow, mature in the thymus.
- CD4 helper cells: recognize antigens presented by MHC class II molecules.
- CD8 cytotoxic cells: recognize antigens presented by MHC class I molecules.
- Activation of T cells requires binding of antigen/MHC complex.
- T lymphocytes release lymphokines.
- T cells regulate macrophage activation and recruitment via lymphokines.
T-Helper Cells
- T helper cells are a type of T lymphocyte that helps activate other immune cells, such as macrophages and B cells.
- Two major subtypes of T helper cells:
- TH1 cells: produce cytokines that promote cell-mediated immunity.
- TH2 cells: produce cytokines that promote humoral immunity.
B-Lymphocytes
- Produced in the bone marrow.
- Differentiate to form either memory B cells or plasma cells.
- Plasma cells produce antibodies.
Natural Killer (NK) Cells
- NK cells are a type of lymphocyte that can kill infected cells and cancer cells.
- NK cells do not require prior sensitization to the target cell.
- NK cells are important for the early innate immune response to infections.
Mast Cells/Basophils
- Basophils are the least common white blood cells in the blood.
- Basophils migrate into tissue to become mast cells.
- Mast cells release histamine and other inflammatory mediators.
Eosinophils
- Common in many allergic inflammatory reactions.
- Effective killers of parasites.
- Phagocytic.
- Major basic protein-MBP: toxic to parasites and contributes to tissue damage, mediate tissue damage.
Granulomatous Inflammation
- Specific form of chronic inflammation.
- Aggregation of macrophages with an enlarged, epithelium-like appearance (called ‘epithelioid’ macrophages), surrounded by a rim of lymphocytes.
- Giant cells: large multinucleated cells formed by fusion of macrophages.
Causes of Granulomatous Inflammation
- Infection (specific types).
- Foreign body.
- Response to tumours.
- Metal/dust.
- Unknown aetiology.
Infectious Causes of Granulomatous Inflammation
- Bacteria.
- Spirochaetes.
- Fungi.
- Parasites.
Tuberculosis
- Type IV hypersensitivity.
- Histological features.
- Culture, PCR, and fluorescent staining methods are used to diagnose it.
Sarcoidosis
- Granulomatous condition of unknown aetiology.
- Young adults, blacks > whites.
- May affect any tissue.
- Non caseating ‘naked’ granuloma.
- Schaumann bodies and Asteroid bodies.
Type IV Delayed Hypersensitivity
- Interactions between CD4 T helper cells and macrophages.
- Macrophages present antigens via MHC II to CD4 helper cells causing their activation.
- T cells produce cytokines.
- Seen in diseases like TB, fungal infection, sarcoidosis.
Morphologic Patterns In Acute And Chronic Inflammation
- Serous inflammation.
- Fibrinous inflammation.
- Suppurative inflammation.
- Ulcers.
- Sinus.
- Fistula.
Serous Inflammation
- Accumulation of thin fluid derived from the blood serum or secretion of fluid from mesothelial lining.
Fibrinous Inflammation
- Accumulation of fluid and fibrin due to increased vessel permeability
- Common locations include the serosal linings of the pericardium, peritoneum and pleura.
Suppurative Inflammation
- Purulent inflammation is a localized proliferation of pus-forming organisms.
- Cellulitis is a spreading type of bacterial infection of subcutaneous tissue.
Abscess
- Localised collection of pus.
Ulcer
- Local defect in an epithelial surface.
Sinus
- Tract lined by granulation tissue leading from a chronically inflamed cavity to a surface.
Fistula
- Track open at both ends, through which abnormal communication between two surfaces is established.
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