Section 1
Preview this deck
Increase in cell size.
Front
| 5 | 0 | ||
| 4 | 0 | ||
| 3 | 0 | ||
| 2 | 0 | ||
| 1 | 0 |
Active users
0
All-time users
0
Favorites
0
Last updated
4 years ago
Date created
Mar 14, 2020
Cards (429)
Section 1
(50 cards)
Increase in cell size.
Define hypertrophy.
Overgrowth of granulation tissue.
What is proud flesh?
Nucleus disappears.
Define karyorrhexis.
When the wound splits open.
What is wound dehiscence?
Usually surgery required with correction of alignment, removing fibrous tissue, possible none grafting and reproducing the haematoma to start the healing process again.
What can be done to heal fibrous union of bones.
Gathering of cells e.g. neutrophils at the site of infections.
Define cellular accumulations.
Overgrowth of scar tissue. This is when there is an overgrowth of collagen.
What is a keloid?
Persistant inflammation without resolution.
Define chronic inflammation.
The tissue is returned to normal.
What is regeneration?
• Haematoma • Soft callous • Hard callous • Remodelling
What are the 4 stages of bone healing?
Cell growth and division (mitosis)
Define proliferation.
Leakage of protein rich fluid (esp. fibrinogen) into the extravascular space.
What is the fluid exudate?
Dermis forms scar. Surface epithelium regenerates.
When skin heals which layer forms the scar tissue and which regenerates?
• Movement (too much, too little) • Infection • Foreign body • Nutrition • Medication - corticosteroids • Other medical conditions - diabetes
What things can cause failure of bone to heal?
Congestion and stasis - loss of laminar flow enabling white cells to come into contact with the endothelial cells.
What is the purpose of the fluid exudate?
Cell/organ kills itself.
Define suicide and apoptosis.
• Nutrition - protein, vitamin C • Diabetes • Steroid medication - anti-inflammatory and slows collagen synthesis • Infection • Blood supply • Mechanical factors - movement • Foreign material
What host factors influence repair in all tissues?
A cell that produces ECM and collagen, important in healing.
What is a fibroblast?
Comorbidity associated with primary damage.
Define collateral damage.
Change of cell type e.g. epithelial cell types change
Define metaplasia.
Primary damage leads to secondary damage.
Define sequential damage.
• 24 hours - blood clots and a scab forms. Neutrophils flood to the site of inflammation. Mitosis of basal epithelium. • 1-2 days - epithelial cells grow along the exposed dermis. • 3 days - granulation tissue in dermis, fibroblast and macrophages at site of injury, neutrophils gone, new capillaries form. • 5 days - fibrous union (collagen fibrils bridge wound), epidermis at pre-incision thickness
Describe the timeline of healing by primary intention.
Progenitor cells from periosteum and bone marrow differentiate within the granulation tissue to produce cartilage.
Describe soft callous.
State of non-replication (important in genetic mistakes e.g. cancer)
Define senescence.
Swelling (from cellular accumulations or cellular release of contents)
Define oedema.
• Formation of new endothelial channels (angiogenesis) • Migration and proliferation of fibroblasts laying down collagen • Deposition of ECM • Maturation and organization of fibrous scar
Outline the process of healing by scarring (granulation tissue)?
Whole chunk of tissue dies due to loss of blood supply (ischemia).
Define infarction.
Well done
Read this stuff
Immediate host response to any form of tissue insult.
Define acute inflammation.
Intracellular degradation of cytoplasmic constituents in lysosomes (autophagosome + lysosome).
Define autophagy.
An innate response to any form of insult. To remove and injurious agent and any damaged tissue.
What is acute inflammation and what is its purpose?
Cell/organ killed.
Define homicide and necrosis.
Tissue comprised of: • New vessels • Fibroblasts laying down collagen • Extracellular matrix
What is granulation tissue?
Nucleus starts to disappear.
Define karyolysis.
Nucleus of cell gets smaller.
Define pyknosis.
With weight bearing the bone framework is orientated to give maximum strength and return the bone to the pre fractures state.
Describe remodeling.
• Non-union - bone ends too far apart • Fibrous union - the bone ends are joined by fibrous tissue, bone not formed.
What are two possible results of failure of bone to heal?
Blood clot forms at fracture. Infiltration by neutrophils and later macrophages (acute inflammation). Haematoma gradually removed and granulation tissue emerges.
Describe haematoma.
Decrease in cell size.
Define atrophy.
• Labile cells - constantly dying and being replaced - epithelial cells. • Stable cells - cells quiescent but can divide in response to stimuli - endothelium, liver, kidney, etc. • Permanent cells - have no capacity to divide - neurons, myocardium.
What are the three types of cells (e.g. dividing capacities)? Give an example.
Surgery; The immediate closure of a surgical field in a multitrauma patient after the major vascular injuries and other sources of life-threatening bleeding have been repaired.
Define damage control.
Formed as ossification of the cartilage occurs.
Describe hard callous.
Endothelial cells become sticky. White cells roll along the endothelial cells finally becoming adhered to the endothelium. The cells then escape through the endothelial wall by a process termed diapedesis. Cells migrate along a chemical gradient provided by C5a and bacterial products (if present).
How is the cellular exudate formed?
Cell replication in numbers to increase organ size
Define hyperplasia.
Tissue unable to return to normal (e.g. connective tissue framework is lost, or non-regenerating cells).
What is scarring?
Other side first
This side first
• Regeneration • Scarring
What are the two outcomes of the acute inflammatory response?
Same as above then: • 5 days - wound contraction (by myofibroblasts) followed by fibrous union.
Describe the process of healing by secondary intention.
• Heat • Pain • Swelling (tumor) • Redness (rubor) • Loss of function
What are the 5 clinical signs of inflammation?
• Primary intention - edges of wounds bought together by suturing. • Secondary intention - large deficit of tissue, wound edges can't be brought together.
What are the two ways that skin heals?
Section 2
(50 cards)
S = fibrous connective tissue (granulation tissue) T = woven bone
This is a histological preparation of an area of non-union in bone healing. What are the tissues labeled S and T?
An inflammatory arthritis developing in response to the deposition of irate crystals within the synovium of joints, ligaments, tendons and soft tissues.
What is gout?
A degenerative disease due most likely to the loss of homeostatic mechanisms within the cartilage.
What is osteoarthritis?
• Haematogenous dissemination from some other focus (fro tissue via blood) or a bacteraemia (in blood) • Spread of infection from an adjacent site to bone • Trauma • Iatrogenic - surgical
How do organisms gain entry into the bone?
Reparative response by remaining cartilage at the edges of a damaged joint. Most common in osteoarthritis by may be seen in other conditions that result in extensive joint damage.
What is an osteophyte?
Inflammation in the bone marrow
What is osteomyelitis?
• Increasing pressure in bone shaft, decreases blood flow → medullary bone dead af • Pus forced through aversion system, gathers subperiosteally → lifts periosteum, removes blood flow →cortical bone dead af (sequestrum) • Involucrum forming • Pus may ooze into soft tissue forming abscess which can reach skin surface → ruptures → sinus → sequesterm extrudes through sinus
Describe chronic osteomyelitis.
• Immune response → inflammation, proliferation of the synovium (=pannus) expands into joint space. • Enzymes related to the inflammation damage eventually erode the underlying cartilage • Underlying bone is exposed and damaged, so the bone surface pitted and irregular
Describe joint changes in rheumatoid arthritis.
Margination of neutrophils by adhesion molecules (selections and integrins)
What process is occurring in this image? What cells and molecules are involved?
A shock absorber during normal joint movement. Distributes weight and prevents bone crushing and crepitus.
What is cartilage?
Dead bone resulting from either pressure within the marrow cavity or due to loss of the blood supply because of lifting of the periosteum (white/pale).
What is the sequestrum?
• An acute phase protein produced in the liver in response to IL6 from macrophages, following tissue insult • Binds to phosphocholine on the surface of dead and dying cells, activates complement • Increases in proportion to the degree of inflammation • Peaks at 48 hours (t1/2 = 18 hours)
What is C-reactive protein (CRP)?
• Loss of proteoglycans (ground substance) - superficial chondrocytes die, deeper proliferate to form clusters. • Fibrillation - dehydration and superficial layer cracks. • Cartilage fragments break off • Cartilage lost in areas of greatest stress • Bone exposed → eburnation (bone polished)
What changes in cartilage occur due to loss of cartilage maintenance?
X = cartilage. Y = new bone. Z = granulation tissue. a = osteoblast. b = chondrocyte.
Name the tissues X, Y and Z and the cells a and b.
Aspirin interfere with uric acid excretion in urine.
Why is aspirin not used as an NSAID in the treatment of gout?
• Primary - cause unknown but usually due to enzyme deficiency with increased production and/or decreased excretion • Secondary - chronic renal disease. increased turnover of cells. Inborn errors of metabolism (Lesch-Nyhan syndrome).
Describe the two classifications of gout.
Hyperextension of the PIP and flexion at the DIP joint with stretching of the velar plate at the PIP and damage to the extensor tendon at the DIP.
What is a swan neck deformity.
Proliferation of the synovial lining cells, inflammatory cells, granulation tissue and fibrous connective tissue.
What is the pannus?
• Joint space occupied by pannus. The cortical bone becomes less dense. • Pannus release inflammatory cytokines that cause loss of articular cartilage and damage to the exposed bone. • Destruction of the adjacent joint capsule/tendons leads to instability and deformity, tendons may rupture • Radial (lateral) deviation of the wrists and ulnar (medial) deviation of fingers
Describe joint pathology of RA.
Painless lumps arising in the subcutaneous tissue of skin in areas which are subjected to pressure. In cases of severe disease. Nodules have a fibrinoid necrotic core which is surrounded by a palisade of macrophages lymphocytes and plasma cells. These nodules may also arise within the synovium.
What is a subcutaneous rheumatoid nodule.
• Infiltration by mononuclear cells (lymphocytes, monocytes, plasma cells) • Tissue damage continues • Attempts at repair
Describe cellular features of chronic inflammation.
• NSAIDs - naprogesic and diclofenac • Colchicine - inhibits neutrophil mobility and activity. • Low dose steroids (if NSAIDs unsuccessful) • Hydration • Medical assessment to reduce risk factors
What treatments are available for gout.
Deposits of urates surrounded by lymphocyte, macrophages and giant cells. Fibrous tissue surrounds the area.
Describe the histology of a tophus.
Secondary intention (may require skin graft).
How will this wound heal?
• Pain relief • Physiotherapy • Immunosuppression (steroids, TNF antagonists)
Describe RA treatments available.
• Normal blue/grey colour → pale blue-pink, due to changes in ground substance • Fibrillation
Describe the changes that have occurred in this cartilage.
By primary intention
How will these lesions heal?
Systemic, chronic inflammatory autoimmune disease. Affects mainly joints - proliferative synovitis with destruction of cartilage, ligaments, tendons and joint capsules leading to destruction and deformity of the joints.
What is rheumatoid arthritis?
- Vasodilation and congestion - Redness - Pus
What are the common features of acute inflammation seen in these photographs?
Persistent inflammation that has been present for a long time. Results from: • Acute inflammation - when inciting agent not removed • De novo - fleeting acute response is replaced by smoldering inflammation
What is chronic inflammation?
Flexion deformity of the proximal PIP joint due to rupture of the central slip of the extensor tendon so that the proximal phalanx pokes through the lateral slips of the tendon. Hyperextended distal joint.
What is a boutinniere deformity?
Acute episode less intense but continuous into chronic. Synovial cartilage thickened, inflamed and hyperplastic → pannus which results in damage to cartilage and subchondral bone → narrowing joint space. Perheral and bony tophi evident with bone remodeling.
Describe chronic (advanced) gouty arthritis.
• Anaemia of chronic disease • Fatigue • Loss of appetite • High CRP and acute phase proteins • Intermittent fever • Weight loss • Subcutaneous rheumatoid nodules
Describe systemic pathology of RA.
• Loss of the joint space due to loss of cartilage • Sclerosis of bone in the weight bearing areas (no bone cartilage) • Subchondral bone cysts • Osteophyte formation
What changes occur to the overall joint in osteoarthritis.
• Cartilage degenerates • Staining changes • Cartilage breaks down, exposed surface becomes frayed (fibrillated), eventually cartilage lost completely
Describe fibrillation of cartilage.
A deposit of crystalline uric acid and other substances at the surface of joints or in skin (e.g. pinna of ear) or cartilage. Urate crystals surrounded by neutrophils macrophages and giant cells.
What is a tophus (pl. tophi)?
New bone laid down beneath the periostem and may, if large enough, encase the dead bone.
What is the involucrum?
• 80-90% of cases caused by Staphylococcal aureus • Others include: - E. coli - Group B strep - Salmonella - M. tuberculosis
Which bacteria usually cause osteomyelitis?
• Broad spectrum treatment initially • Sensitivity test reveals correct antibiotic to use • Relieve pressure surgically and debride dead tissue and pus (if no clinical improvement after 24-48 hours)
How do we treat osteomyelitis?
Prevent instability of joints.
What are the roles of supporting ligaments and joint capsules?
- Swelling - Reddness - Pus
What features of acute inflammation are seen in this photograph?
Over time microtophi form in synovial membrane and cartilage, physical change in environment → solubility change of stored irate crystals → leak into synovial fluid → acute painful gout (typically in the hallux).
Describe acute gouty arthritis.
- Congested vessel (big red area in middle) - Background of stringy proteinaceous exudate - Neutrophils
Describe abnormalities seen in this section of subarachnoid space with acute bacterial meningitis.
Undiagnosed hyperuricaemia that may persist for years before the onset of symptomatic gout.
Describe asymptomatic gout.
Non-union. Fractured bone ends in both the tibia and fibula have not healed together.
5 months after an operation this x-ray is taken, what has occurred?
Small fractures occur in articulating bone. Joint fluid forced under pressure into subarticular space. The fluid incites a host response and become surrounded by a fibrous capsule.
Describe cyst formation in osteoarthritis.
• Neonates - metaphysis, epiphysis and joint space (growth and great blood flow here) • Children - ends of log bones (inc. metaphysis), blood vessels no longer penetrate to epiphysis • Adults - spinal column or elsewhere within the axial skeleton (most common in most vascular areas)
How do the common sites of osteomyelitis change with age?
Reoperate and debride the connective tissue and create a new soft callus.
What must be done to ensure healing of a non-uninous fracture?
Lines the non-articulating aspects of the joint. Secretes synovial fluid, which acts as a lubricant in the movement process.
What is synovium?
• Multifactorial: - Environment - Genetic - Immune system • CD4 +ve cells (TH1 and TH17) are a major source of cytokines inducing inflammation • Antibodies to citrullinated peptides result in immune complex deposition in joints. Diagnostic marker. • Genetic - HLA-DRB1 locus frequently in RA, non-HLA also important. • 80% of patients have rheumatoid factor which is an IgM antibody against the Fc portion of self IgG.
Describe the pathogenesis of RA.
Section 3
(50 cards)
• Neisseria meningitidis
Which bacteria causes meningitis in adolescents?
Originates from choroid plexus and circulates in the subarachnoid space.
Where does CSF originate and in which space is it found?
A lumbar puncture
What is the diagnostic test for meningitis?
Less dramatic: • Headache • Feeling unwell • Confusion • Vomiting
What are the signs and symptoms of chronic meningitis?
• Tuberculosis • Spirochetes • Fungi • Amoebe • Chemical
What sort of infectious or other agents cause chronic meningitis?
Fibrinous protein exudate and a cellular exudate comprising neutrophils and macrophages.
This is fluid aspirated from an infected joint. What will this show when examined under a microscope?
Varus deformity (bowed legs, toward the midline). Quadriceps muscle wasted.
Describe the abnormality in these knees.
• Bacteraemia • Trauma • Surgury
How do organisms gain entry to a joint cavity?
Supine patient with hip flexed 90 degrees will have rigidity and pain preventing full extension of the knee.
What is Kerning's sign??
• Bacterial (pyogenic) • Viral • Chemical
What sort of infectious or other agents cause acute meningitis?
Surgical drain and irrigate the joint and systemic antibiotic therapy. Failure to treat adequately will lead to serious joint damage.
How do we treat septic arthritis?
Articular cartilage on both is pitted with erosion of the cartilage exposing the underlying bone on the right femoral condyle.
Describe this knee joint (patella above, femur bellow) from an osteoarthritis patient.
Loss of typical bluish staining. Small islands of hyperplasia of the chondrocytes on the right. On the left the surface has become frayed which is termed fibrillation. Bits of cartilage may dislodge from here to form 'joint mice'.
Describe the changes in this cartilage. Left is superficial cartilage and right is an area of cartilage adjacent to an area of bone.
Nodules of uric acid crystals in soft tissues (found commonly in the ears).
What is a soft tissue tophus in gout?
• E coli • Group B Streptococci • Mycobacterium Tuberculosis
Which bacterial species cause meningitis in neonates?
• Organisms enter CSF • Release of cytokines from astrocytes and microglia • Changes to the blood/brain barrier result in increased permeability leading to vasogenic oedema and brain swelling (increased intracranial pressure, unconsciousness and vomiting) • Acute inflammatory exudate forms in the subarachnoid space
Describe the pathophysiology of meningitis.
Passive flexion of the neck causes flexion of both the hip and knee.
What is Brudzinski's sign?
• Ziehl Nielsen staining • PCR/latex agglutination detect microbial antigens
What are the main processes of identification in suspected unusual organisms in CSF specimens.
When the CSF becomes contaminated by infective or irritating agents, inflaming the arachnoid, pia and cerebrospinal fluid within the subarachnoid space.
What is meningitis?
Material scraped out of a tissue for examination.
What is curretted material?
PCR and/or grown on special culture medium.
How do you identify chronic bacterial tuberculosis.
• Clear • Pressure: 6-18 cm H2O • Cells: 0-6 cells/ml. Usually mononuclear - 75% lymphocytes. • Protein: 0.2-0.4 g/L • Glucose: approximately 1/3 of serum glucose
Describe the properties of normal CSF.
Infection within the joint cavity leading to acute inflammation.
What is septic arthritis?
• Streptococcus pneumoniae • Listeria monocytogenes
Which bacterial species cause meningitis in elderly?
Several layers of hyper plastic synovium (top arrow). Chronic inflammatory infiltrate predominantly plasma cells (middle arrow). Fibrosis (bottom arrow).
Describe the histology of this greater magnification image of the pannus.
• Cloudy (not purulent) • Pressure: mild-moderate • Cells: increased, mainly mononuclear • Protein: mild increase • Glucose: mild-moderate decrease • Gram stain: negative
Describe the properties of CSF in chronic bacterial tuberculosis.
• Clear-cloudy • Pressure: mild-moderate • Cells: increased, mainly mononuclear • Protein: moderate increase • Glucose: normal range • Gram stain: negative (no bacteria)
Describe the properties of CSF in acute aseptic meningitis.
Chronic tophaceous gout (gout with formation of uric crystals). Bony erosions with loss of joint space and complete destruction of joints. Arrow indicates a tophi - a calcification formed as a result of new bone laid down but the periosteum.
Describe the pathological process that have occurred in this image. What is indicated by the arrow?
• Plasmodium
What protozoan can cause meningitis?
• Enteroviruses • Herpes simplex type 2 • Varicella zoster • Mumps
What viruses can cause meningitis?
• Gram stain • Culture • Protein and glucose assessment
What are the main processes of identification in routine CSF specimens.
• Cryptococci • Candida
What types of fungi can cause meningitis?
• Headache • Stiff neck • Kernig's sign - straight leg raising stretches meninges and causes pain • Fever • Anorexia -> nausea and vomiting • Late - confusion and loss of consciousness (intracranial pressure)
What are the signs and symptoms of acute meningitis?
CSF inoculated by viruses. Aseptic as not found on gram stain. CSF contains mononuclear cells (lymphocytes (T cells, B cells, NK cells) and monocytes)
Describe aseptic meningitis.
Red material is residual pannus which is inflamed. The cartilage has eroded and damage to the underlying bone due to the overlying pannus.
What is the red material in this image? What has happened to the cartilage?
• Acute inflammatory exudate within the subarachnoid space. • Neutrophils predominate. • Stringy background is fibrin (converted from fibrinogen which is the major protein in the fluid exudate) • Vessels are dilated and congested
Describe the histology of the subarachnoid space in bacterial meningitis.
• Haemotogenous • Direct (trauma) • Local extension (sinusitis, osteomyelitis) • Iatrogenic • Along nerves (rabies, herpes zoster)
What are the 5 routes of CNS infection??
Ligament of head of femur remains. Loss of cartilage and polishing of the exposed bone = eburnation. Lumpy osteophytes seen around base of head.
Describe this femoral head from and osteoarthritic patient.
• Creamy colour (turbidity) • Increased pressure • Increase cell count (almost 100% neutrophils in bacterial meningitis) • Increased inflammatory proteins • Descreased glucose as inflammatory cells consume it • Gram stain: positive (bacteria present)
Describe the properties of CSF in acute bacterial meningitis.
Fleshy projections of synovium with the darkly staining areas representing chronic inflammatory cells (mostly plasma cells).
Describe the histology of this pannus.
• Pia mater • Arachnoid mater • Dura mater
What are the three layers of the meninges?
• Haemophilus influenzae
Which bacteria causes meningitis in infants?
• Septic • Aseptic • Chemical or non-infectious
What are the three types of meningitis?
Osteoarthritis: - loss of joint space medially - Sclerosis of the adjacent bone - Osteophytes
What abnormalities are seen on this x-ray?
• Swollen • Marked vasocongestion and dilation of the vessels • Pus in the subarachnoid space especially around the brain stem and cerebellum
Describe the gross appearance of the brain in meningitis.
The bone at the top is dead, the cellular tissue bellow is an acute inflammatory exudate of pus due to the infection present.
Describe the pathology of the bone in this image.
Subarachnoid infection is caused by bacteria in the CSF.
Describe septic meningitis.
Staphlococcus aureus
Which bacteria most commonly causes septic arthritis?
• Haemophilus influenzae • Streptococcus pneumoniae • Niesseria meningitidis
What causes of bacterial meningitis can be dramatically reduced with vaccination?
A = cartilage. B = cysts with fibrous wall. C = sclerotic bone. D = eburnated surface.
Identify the structures A, B, C and D.
Section 4
(50 cards)
• Removal of the underlying cause (e.g. gram negative bacteria - antibiotics) • Replace the coagulation products - Antibiotics - Fresh frozen plasma - Coagulation products - Packed red cells
How is DIC treated?
- Small nodules - Granulomata - Features of tuberculous meningitis
Describe the abnormalities seen in this image.
• Recovery • No significant changes occur to the brain
Describe the outcome of viral meningitis.
• Unclear but thought to be related to the adrenal vessels sustain endothelial injury due to endotoxins • Proposed that an increased in adrenal venous pressure may result in hemorrhage • ACTH is released as part of the shock response leading to increased blood flow and platelet aggregation in adrenal veins.
Describe the Cause of WF Syndrome.
A rash of purple spots on the skin caused by internal bleeding from small blood vessels.
What is purpura?
• Acute adrenal insufficiency due to massive hemorrhage into the adrenal glands • Part of the spectrum of shock esp. that associated with N. meningitides but also pneuococcus and H. influenza
What is Waterhouse-Friederichsen Syndrome?
Disseminated intravascular coagulation: • Scattered, diffuse, exaggerated thrombosis in microcirculation due to: - Exposure of sub-endothelial collagen - Release of tissue thromboplastin (tissue damage) • Activates both clotting cascade and fibrinolytic system at same time
Define DIC.
• Non-propagating organisms in blood • Minimal/no mediators, toxins • Minimal/no endothelial or tissue damage and coagulation • DIC not possible
Define bacteremia.
• Prostacylin • Nitrous oxide • ADPase
What three substances prevent platelets adhesion and activation (antiplatelet)?
Giant cell within a granuloma. Surrounding epithelioid cells. T- lymphocytes further out.
Describe the histology of this section of granulation tissue taken from the subarachnoid space in chronic tuberculosis meningitis.
Inactivates thrombin.
Describe the anticoagulation mechanisms of anti-thrombin.
Prevents initiation of tissue factor pathway.
Describe the anticoagulation mechanisms of tissue factor pathway inhibitor.
Cellular and tissue damage has occurred.
What is the irreversible stage of shock?
• Newborn/infant - 20-30% • Children 2% • Adults 19-37%
Describe the percentages of mortality due to meningitis in newborns/infants, children's and adults.
Bilateral haemorrhagic necrosis of the adrenal glands in child with N. meningitides septicaemia.
Describe this image.
Turn off coagulation.
Describe the anticoagulation mechanisms of thrombomodulin, protein C and protein S.
Compensatory mechanisms maintain organ function.
What is the non-progressive stage of shock?
• Tissue factor pathway inhibitor (TFPI) - Tissue factor and FactorVIIa inhibitor • Protein C system - Factor IXa, VIIIa, Xa and Va inhibitor • Antithrombin III - Factor Xa, Va and IIa (thrombin) inhibitor
What are the three anticoagulation pathways?
• Inflammation - vascular constriction • Platelets - adhere via vWF an exposed collagen - aggregate into bulky plug • Tissue factor - pro-coagulation effects • Antiplasmins and plasminogen activator (t-PA) inhibitors - antifibrinolytic effects.
Describe how endothelial injury or activation promotes thrombosis.
• 150-400x10^9/L
What is the normal range of platelets in blood?
• Non-progressive • Progressive • Irreversible
What are the three stages of shock?
Waterhouse-Friederichsen syndrome. Several fulminating intra adrenal haemorrhage. A complication of severe shock
Describe this image.
A substance secreted by endothelial cells which binds to the sub endothelium. Loss of endothelial cells during trauma exposes vWF bound to collagen and platelets bind via glycoprotein receptors (Gp1b).
What is von Willebrand Factor (vWF)?
Renal glomerulus contains fibrin thrombi. This is the result of DIC with fibrin thrombi forming in the capillary network throughout the body. As a result the GFR would be compromised and she would go into renal failure.
This is a renal glomerulus with a trichrom stain which shows protein as bright red. What protein is this? Describe the pathogenesis.
• Vasodilation leading to low peripheral resistance, decreased blood pressure • Decreased myocardial contractility and decreased blood pressure • Endothelial damage, due to endotoxins, cytokines or decreased perfusion leakage. decreased volume and blood pressure • DIC especially in microcirculation - get micro thrombi, decreased perfusion (blood delivery to capillary bed)
Describe the physiological effects of septic shock.
Shed from megakaryocyte in bone marrow.
How are platelets produced?
Granulomas within the subarachnoid space. Arrow points to caseous necrosis (cheese like). Chronic inflammatory infiltrates and fibrosis.
Describe the histology of this section of subarachnoid space in chronic tuberculosis meningitis.
Dermal haemorrhaging due to vascular damage. Damaged endothelium leads to thrombus and necrosis of the skin.
Describe the appearance of the skin in this image.
Tissue type plasminogen activator (t-PA) (activates plasminogen to plasmin which breaks down fibrin).
What substance breaks down fibrin (fibrinolytic)?
• Disc-shaped • Granular • Anuclear
Describe the structure of a platelet.
• Exotoxins on bacterial surface released (mainly Staph. aureus and Strep, progenies) = super antigen • Binds to MHCII on antigen presenting cells and T cells (up to 10% T cells activated) • Causes release of massive quantities of cytokines (cytokine storm), causes septic shock
Describe septic shock from gram positive bacteria.
• Exhaustion of clotting factors, platelets, fibrinogen and protein C with production of D-dimers from fibrin breakdown. • Bleeding from drip sites, areas of trauma and areas of necrosis.
Describe the outcome of DIC.
• Propagating bacteria releasing toxins (sepsis) • Maximal mediators, toxins • Maximal endothelial and tissue damage and coagulation • DIC possible.
Define septicaemia.
• Cardiogenic • Hypovolemic • Neurogenic • Anaphylactic • Septic - especially due to gram positive bacteria
What are the five types of shock?
Binds to and stabilises FVIII, preventing it's proteolytic degradation.
What is the function of circulating vWF?
Autosomal dominant.
Describe the inheritance of vW disease.
• Adhesion, activation and shape change • Secretion (release reaction) • Aggregation - forming the primary platelet plug
Describe the changes that occur to platelets when they come into contact with collagen or vWF.
• Vasoconstriction • Platelets • Coagulation
What are the three components of haemostasis after hemorrhage?
Prevent bleeding when it is expected e.g. surgery give vWF, heavy menstrual bleeding use contraceptive pill.
How is vW disease treated?
• Lipopolysaccharides which are part of the bacterial wall • Act as endotoxins • These bind and activate neutrophils and macrophages with releases of cytokines (IL-1, 6, 8 and TNF-alpha plus nitrous oxide and platelet activating factor) • Severity of condition relates to amount of cytokines released
Describe septic shock from gram negative bacteria.
• Anti-thrombin • Thrombomodulin • Protein C • Protein S • Tissue factor pathway inhibtor
What substances have anticoagulation effects?
- Brain is swollen - Vessels are dilated and congested - There is pus in the subarachnoid space - The features are of acute inflammation
Describe the abnormalities in this image.
Tissue hypoperfusion with worsening circulation and metabolic functions.
What is the progressive stage of shock?
Clotting disease caused by vWF disorder. 1 - quantitative (low vWG concentration), most common. 2 - qualitative (poor vWF function) 3 - quantitative (homozygous, complete absence of vWF), most rare, but most severe. Platelet type - vWF normal but platelets have defective receptors.
What is von Willebrand disease and what are the four types?
Treating the endothelial-coagulation-multiorgan dysfunction: • Replace protein C, helps stop the action of FVa and FVIIIa and maintains fibrinolytic breakdown of intravascular fibrin • Protein C also provides signals to tissue cells that help to reverse the mutliorgan dysfunction • In fatal cases protein C may be well bellow 10% of normal.
Describe the newer approach to treating DIC.
Neutrophil on the right. Many gram negative diplococci - this is neisseria meningitis.
Describe what is seen in this gram stain taken from a blood sample of a patient with DIC.
Large gene with many possible mutations instead test bleeding times of 1st degree relatives.
Why is genetic testing not done for vWD?
Purple structure is a disrupted neutrophil, with smaller diplococci bacteria seen. Background is RBCs with a lack of platelets.
Describe what is seen in this image taken from a blood sample of a patient with DIC.
Exudate may become organized leading to fibrosis within the subarachnoid space • Fibrous bands around cranial nerves leading to palsies (paralysis and tremors) • Blockage of CSF flow leasing to hydrocephalus • Vasculitis of vessel supplying outer surface of cortex leading to cortical infarction • Epilepsy
Describe what occurs in meningitis if treatment is delayed.
Thrombosis of the dermal vessels and vascular collapse with a combination of necrosis and bleeding.
How does meningococcus sepsis in children cause purpura and DIC?
Section 5
(50 cards)
Platelets when activated. Increases aggregation via GPIIb-IIa
What other cell secretes vWF and when?
• Generation of thrombin which converts fibrinogen to fibrin • Fibrin polymerises to form a clot and is stabilized by FXIII
Describe the common pathway where the two pathways meet up.
A systemic illness due to immune mediated (autoimmune) damage to connective tissue.
How is acute rheumatic fever caused?
1 - platelet receptor activated by; collagen, vWF, ADP, TXA2, thrombin, serotonin or adrenaline 2 - platelet secretes granules: • Dense granules - ADP (for activating platelets) and serotonin (for platelet activation and vessel constriction) • Alpha granules - contain vWF, fibrinogen, factor V, platelet factor 4, and more 3 - Cyclooxygenase pathway activated, amplifies aggregation, activates more platelets and constricts vessels 4 - GPIIb and GPIIIa activated, fibrinogen or vWF binds and platelets aggregate.
Describe platelet secretion (release reaction).
Same as for atherosclerosis: - High cholesterol - Hypertension - Smoking - Diabetes - Low exercise - etc
What are the risk factor of calcific aortic sclerosis?
Platelet aggregometry.
What is a third test possible to measure platelet function?
A disorder characterized by rapid, uncoordinated jerking movements primarily affecting the face, hands and feet
What is Sydenham chorea?
- Calcific aortic sclerosis - Or calcification of the mitral valve annular ring
Give an example of aging/wear and tear valve disease.
Coagulation factros II, VII, IX and X. Coagulation inhibitor proteins C and S.
What clotting factors and coagulation inhibitor proteins does vitamin K carboxylate (activate)?
Production of coagulation factors (and carboxylation of vit. K dependent factors), platelet production.
What is the role of the liver in haemostasis?
Mitral valve prolapse with myxomatous degeneration.
Give an example of valve disease of unknown pathogenesis.
A systolic murmur +/- a diastolic murmur and eventually left ventricular myocardial hypertrophy.
What clinical signs are produced by the calcific aortic sclerosis?
International Normalized Ratio, used to standardise bleeding time by the sensitivity of the tissue factor in a bleeding analysis test.
What is the INR and how is it used?
Group A β haemolytic Streptococcal pharyngitis.
Acute rheumatic fever follows 2-3 weeks after which infection?
Tells us why we are getting poor APTT or PT. Patients blood is mixed with normal blood. If patients poor bleeding time is due to inhibitor of coagulation in blood clotting will not be or only be slightly improved. If patients poor bleeding time is due to lack of factor(s) in blood factors from normal blood will correct clotting time to normal.
What is a mixing study for APTT and PT?
A valve does not open properly and obstructs the forward flow of blood.
What is valve stenosis?
Tissue factor pathway. Most important, triggered by tissue injury.
Describe the extrinsic pathway of coagulation.
In plasma. Activated by shearing stresses and binding to foreign surfaces.
Where is vWF found in an inactive form and how is it activated?
• Blood pumped through capillary coated with platelet activators (collagen-adrenaline, collagen-ADP) • The time required to occlude (block) the capillary is a measure of platelet function
How does a platelet function analyser (PFA-100) measure platelet function?
If the spleen is enlarged (i.e. infection) it will pool more platelets reducing the blood concentration.
What role can the spleen play in thrombocytopenia?
- Congenital - Aging/wear and tear - Aquired - Unknown
What are the 4 pathogenesises of valve disease?
Length of extrinsic pathway to clot formation - 8-11 seconds.
What is the Prothrombin Time (PT) and what is the normal range?
Generally clinically silent but may cause stenosis, regurgitation and arrhythmias.
What clinical signs are produced mitral valve calcification (calcification of the mitral valve annular ring)?
A characteristic but uncommon non itchy rash.
What is erythema marginatum of the skin?
Where the valve cusps come together.
What is a commissure?
Time for conversion of fibrinogen to fibrin once thrombin is produced (common pathway) - 12-18 seconds.
What does Thrombin Clotting Time (TCT) measure and what is the normal range?
The valve does not close properly resulting in back flow of blood into the chamber of origin.
What is a regurgitant/incompetent valve?
Painless, firm collections of collagen fibers over bones or tendons. They commonly appear on the back of the wrist, the outside elbow, and the front of the knees.
Why are subcutaneous nodules produced in acute rheumatic fever?
- Acute rheumatic fever - Chronic rheumatic heart/valve disease
What are the two types of rheumatic heart disease?
Antibodies to Streptococcal M protein produced in approx. 3% individuals, cross react with connective tissue and other antigens systemically (esp. heart, joints and CNS). Additionally CD4+ T cells specific to Streptococcal peptides react with self antigens in the heart producing cytokines and activating macrophages. Causes inflammatory response.
How does group A β haemolytic Streptococcal pharyngitis cause rheumatic fever?
- Rheumatic heart disease - Or bacterial endocaridits
Give an example of acquired valve disease.
Length of intrinsic pathway to clot formation - 22-34 seconds.
What does Activated Partial Thromboplastin Time (APTT) measure and what is the normal range?
Degeneration of connective tissue.
What is myxomatous degeneration?
Contact activation pathway. Role in inflammation and infections.
Describe the intrinsic pathway.
Increased work load to the left atrium leading to left atrial hypertrophy and dilation.
What changes are related to an abnormal mitral valve?
70-100
At what age is calcific aortic sclerosis most common?
Bicuspid aortic valve
Give an example of congenital valve disease.
Standardisation issues.
Why is bleeding time not often performed anymore?
Well done :)
Look at this diagram summarizing coagulation.
Mitral and aortic.
What are the two most commonly affected valves?
Pancarditis (infection of whole heart): - Endocarditis (endocardium) - Myocarditis (myocardium) - Pericarditis (pericardium)
What effects does acute rheumatic fever have on the heart?
Production of bone matrix proteins which become calcified. Calcified martial fills and protrudes from the sinuses of valsalva (aortic sinus). Valve becomes rigid, results in stenosis and some regurgitation. Commissures not involved.
Describe the pathogenesis of calcific aortic sclerosis?
Transport across placenta limited. Stores depleted 2-4 days after birth. Breastmilk has low levels. Lack of bowel microflora to make vitamin K.
Why are babies at risk of vitamin K deficiency?
- Pancarditis - Migratory polyarthritis of large joints - Subcutaneous nodules - Erythema marginatum of the skin - Sydenham chorea
What clinical signs are seen in acute rheumatic fever?
- Inflammation and fibrinoid necrosis occurs in the CT beneath the endocardium. Results in swelling. As valves move, endothelium of valve cusps and chord tendineae are damaged. - Verrucae form; small 1-2mm sterile platelet thrombi in the areas of damage along the lines of closure of the valve and chordeae tenineae.
Describe the effects of endocarditis in acute rheumatic fever.
• Substance produced by the cyclic-oxygenase pathway in activated platelets • Amplifies aggregation • Activates more platelets • Constricts vessels
What is thromboxane A2 (TXA2)?
- 5-14 years old (mostly 9-11) - Associated with lower socioeconomic status - Associated with Māori and Polynesian populations
Describe the demographic epidemiology of rheumatic heart disease incidence.
• Activated Partial Throboplastin Time (APTT) • Prothrombin Time (PT) • Thrombin Clotting Time (TCT)
What tests are available to test coagulation.
Aggregation receptor (GpIIb/IIIa) binds to vWF and fibrinogen - released from platelets and circulating in plasma.
Describe platelet aggregation.
Increased work load to the left ventricle leading to myocardial hypertrophy.
What ventricular changes are related to an abnormal aortic valve?
Section 6
(50 cards)
Vascular cell adhesion molecule-1.
What does VCAM-1 stand for?
- Aortic valve - Commissures are normal - There are calcified nodules within the sinus of valsalva - This would lead to a stiff valve and the presence of a murmur = Calcific aortic sclerosis
Describe the pathology of this image.
- Tunica intima - Tunica media - Tunica adventitia
What are the three layers of a blood vessel?
Bacteraemia of virulent organisms. Bacteria bind to endocardium → inflammation and formation or large friable vegetations. Rapid growth with valvular damage, spread to adjacent myocardium, possible access formation in the systemic emboli.
Describe the pathogenesis of acute bacterial endocarditis.
Mitral valve deformity known as fish mouth or button whole. The commussures are fixed and the valve edges distorted such that the valve cannot close. Small thrombi are present on the upper surface.
Describe this image.
The result of deposition of fatty material within the intima of muscular and elastic arteries. Athero = gruel, sclerosis = hardening.
What is atherosclerosis?
- Hyperlipidaemia - Hypertension - Diabetes - Cigarette smoking - C reactive protein
What are the controllable risk factors for atherosclerosis?
Infection of the endocardium and particularly of valves of the heart.
What is infective endocarditis?
Infection of a normal valve or abnormal/scarred valve.
What is acute endocarditis?
Soft often necrotic centre (cell debris, cholesterol crystals, foam cells, calcium) with overlying fibrous cap (smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularisation)
Describe the structure of a mature atherosclerotic plaque.
Subacute: - Insidious onset - Low virulence organisms - Damaged valve - Low grande chronic infection Acute: - Sudden onset - High virulence organisms - Normal/abnormal valve - Destructive rampant infection
Sort the descriptors into subacute or acute bacterial endocarditis: - Insidious onset or sudden onset - Low or high virulence organisms - Normal/abnormal valve or abnormal valve - Destructive rampant infection or low grade chronic infection
Pale areas of infarction in the kidney. Darker areas of reddy/brown granulation tissue. Associated with abscess formation as a result of septic emboli.
What pathology is evident in this photograph?
- Aneurysm and rupture - Occlusion by thrombus - Critical stenosis (occlusion by plaque)
What are the three possible outcomes of atheroscleosis?
- Valve cusps are thickened - Annular calcification with nodules as indicated by the arrows = Mitral annular calcification
What is wrong with this mitral valve?
Inflammation of the CT leads to sterile fibrinosus exudate -> pericardial effusion.
Describe the effects of pericarditis in acute rheumatic fever.
- Fever - Malaise - Tiredness - Loss of appetite (super general! :/)
What are the clinical signs of acute bacterial endocarditis?
- Staplococcus aureus - Streptococcus pyogenes
Which virulent organisms cause acute bacterial endocarditis?
- Mainly oral commensal organisms (infection due to dental or surgical procedure) - Infection elsewhere
What are the major sources of the bacteraemia leading to acute bacterial endocarditis?
Weakened due to a decrease in oxygen supply and migrating SM cells.
What affect does an atherosclerotic plaque have on the underlying media?
- Activation of recruited monocytes and macrophages, ingesting lipids and become foam cells - Cytokine production - T cells and macrophages stimulate a chronic inflammatory state - Results in growth factor release with ECM production and smooth muscle proliferation - Smooth muscle cells may migrate from media or develop from progenitor cells recruited from the blood
Order these events chronologically in the pathogenesis of atherosclerosis: - Results in growth factor release with ECM production and smooth muscle proliferation - T cells and macrophages stimulate a chronic inflammatory state - Smooth muscle cells may migrate from media or develop from progenitor cells recruited from the blood - Activation of recruited monocytes and macrophages, ingesting lipids and become foam cells - Cytokine production
- Increases acute phase proteins - Increased leucocytes - Increased ESR
What blood tests are indicative of acute bacterial endocarditis?
Intercellular adhesion molecule-1.
What does ICAM-1 stand for?
- Vasodilator - Antinflammatory properties - Limits expression of VCAM-1 (vascular cell adhesion molecule-1).
What are three functions of NO in blood vessels?
There is marked left ventricular hypertrophy as a consequence of a stenotic and regurgitant valve.
This heart would have had a stenotic aortic valve, what is the pathology?
- Chronic aortic valve damage - Distortion of valve cusp - Fusion of commissures
Describe this image.
Intima. Will encroach on the lumen with time as apposed to deeper into the wall.
What layer(s) of a blood vessel are mature plaques found in?
Mitral valve is normal. There is one very large and several small vegetations present on the mitral aspect of the valve cusps. This is an acute bacterial endocarditis. Having formed on a normal valve the infecting organism must be high virulent e.g. S. aureus.
Heart of a previously healthy adult. What is the pathogenesis?
The valve cusps are thickened and distorted. There is a fusion of at least one commissure. The valve would be stenotic and regurgitant.
What is wrong with this aortic valve?
A - valve leaflet. This is thickened and boggy at the edges. B - cordae tendinae C - papillary muscle D - verrucae along lines of closure
The heart is opened showing the mitral valve, what do the letters indicate?
- Age - Male gender - Family history - Genetic inheritance
What are the uncontrollable risk factors for atherosclerosis?
Mitral valve with: - Thickened shortened cordae tedineae - Fibrotic thickened distorted valve cusp - Valve will be stenotic and regurgitant
Describe this image.
Left atrium volume is enlarged. The muscle mass will be increased. Left atrial hypertrophy but with dilation this the walls appear thin.
Describe the pathology of this heart from a patient with mitral valve disease.
Small blood vessels that supply the smooth muscle of larger blood vessels.
What are vaso vasorum?
- Vascular endothelial cells - Lymphocytes - Monocytes/macrophages - Smooth muscle cells
What cells are involved in the pathogenesis of atherosclerosis?
- Embolism of fragments of the vegetations - Rupture of the valve and adjacent myocardial abscess (usually in acute endocarditis)
What complications can occur as a result of acute bacterial endocarditis?
Valves stenotic and regurgitant: - Blood flow damages endothelium on top of (up stream) of valve - Small platelet fibrin form and low virulence organisms from bacteraemia infect them. Inflammatory response follows resulting in large friable vegetations comprising thrombotic material, inflammatory cells and bacteria.
Describe the pathological effects of acute bacterial endocarditis.
Haemorrhage into the plaque: - From the neovascularisation at the shoulders of the plaque - From rupture of the fibrous cap
Along with occlusion by the plaque or by thrombus what is the third way that an occlusion may occur?
Infection of a previously damaged valve or congenital valve.
What is subacute endocarditis?
Ischaemia: - Myocardial infarction - Cerebral infarction - Peripheral vascular disease - Gangrene of extremities
What affect does partial or total occlusion of a vessel have on distal tissues in the heart, brain, vessels and distal tissues?
Layers of elastic tissue in muscular arteries. - Internal elastic lamina between intima and media - External elastic lamina between media and adventitia
What are the two elastic lamina and where are they found?
Collections of T lymphocytes, plasma cells and activated macrophages called Antischkow cells. These are also known as caterpillar cells due to the characteristic clumping of the nuclear chromatin.
What are Ashcoff bodies?
- Risk factors - Endothelial cell damage - Expression of VCAM-1 and ICAM-1 - Binding of T lymphocytes and monocytes - T lymphocytes and monocytes enter intima - Influx of LDL - LDL oxidation - Activation of macrophages within the intima
Order these events chronologically in the pathogenesis of atherosclerosis: - Binding of T lymphocytes and monocytes - Expression of VCAM-1 and ICAM-1 - Influx of LDL - T lymphocytes and monocytes enter intima - Endothelial cell damage - Activation of macrophages within the intima - LDL oxidation - Risk factors
Scarring of the endocardium leads to: - thickened/distorted valve cusps (particularly closing edge) - Fusion of commissures - Thickening, fushion and shortening of chordae tendineae - All affect valve function (stenosis and regurgitation -> ongoing valve wear and tear)
Describe the pathological effects of chronic rheumatic valvular disease.
Chordae tendinae are markedly shortened and thickened as is the edge of the valve cusp. The effect would be to prevent adequate closure of the valve leading to incompetence. The thickening of the leaflet leads to stenosis.
This image shows the chordae tedninae of the mitral valve. What is the pathology? What effect will this have on valve function?
Areas of inflammation, Aschoff bodies and muscle necrosis. Decreases muscle contractility (greatest cause of ARF death).
Describe the effects of myocarditis in acute rheumatic fever.
When inflammation subsides the lesions from autoimmune reactions heal. The connective issue is unable to regenerate so healing is by fibrosis. Scarring will occur in the all layers of the heart. Endocardial scarring changes valve shape and therefore valve function.
Describe healing of acute rheumatic fever.
Blood vessel formation stimulated by cytokines at the shoulders of the cap of the plaque.
What is neovascularisation?
Haemorrhagic infarct in the MCA territory of the brain. Associated with abscess formation as a result of septic emboli (emboli → stroke → ischaemic necrosis)
What is the pathology evident in this photograph?
Mitral valves cusps thickened and shortened with a fish mouth/button hole deformity. The commissures are fused. Small thrombi are present on the upper surface of the valve. A small thrombus is present in the atrial appendage of the left atrium.
What is the pathology of the valve indicated. What are the lesions indicated at a and b?
A - thickened chordae tendinae B - thickening and distortion of the valve cusp as well as fusion of the commisure C - myocardial hypertrophy D - a large friabel vegetation representing subacute blood flow through a damaged valve. As a result of the rheumatic valve disease abnormal blood flow would result in further damage. Turbulent back flow of blood leads to superficial endothelial damage with the formation of platelet/fibrin thrombi. Bacteria colonize the thrombi and a vegetation develops.
Heart of 59 year old man with history of rheumatic valve disease, resulting in a lifetime of ongoing damage. What is the pathology seen in this photograph and the structures seen at A, B, C and D.
Section 7
(50 cards)
Same as atheroslcerosis: - Smoking, diabetes, hyperlipidaemia and hypertension - Age, male, family history, sedentary life style, obesity, use of oral contraceptives.
What are the risk factors of ischaemic heart disease?
Narrowing of lumens and thickened walls of small arteries and arterioles with aging and in hypertension.
What is arteriosclerosis?
Patients present with symptoms and signs of myocardial infarction without ECG changes. Troponin however elevated. Often falsely diagnosed as unstable angina.
What is non-ST elevation myocardial infarction (non-STEMI)?
Blood within the abdominal cavity. Large bulge in the middle is an aortic aneurysm.
Describe what can be seen in this image.
Mural thrombus at top - will be filling the aneurysm. Atherosclerotic debris bellow this. Medial bellow black elastic later will loss of elastin and fibrosis. Bottom is connective tissue of adventitia.
Describe the pathological features of this section of aorta from an aortic aneurysm.
<12 hours: oedema, hemorrhage 12-24 hours: nuclear pyknosis, myocyte hypereosinophilia 1-3 days: loss of nuclei and striations, increased nutrophils 3-7 days: disintegration of myofibres, dying neutrophils, some macrophages 7-10 days: phagocytosis, early granulation tissue 10-14 days: granulation tissue with early collagen formation 2-8 weeks: increasing collagen, decreasing cellularity
Describe the microscopic changes in MI with time.
Rupture of the fibrous cap of an atherosclerotic plaque. There has been formation of an occlusive thrombus due to the exposure of collagen
Describe what has occurred at the arrow.
Greater than 75% obstruction.
At what percentage of obstruction is maximal blood flow impaired?
<12 hours: none 12-24 hours: some mottling - dark/pale patchiness 1-3 days: pallor of infarct area 3-7 days: hyperemic border to pale infarct 7-10 days: pale and soft with clear redden margin 10-14 days: soft and shrinking infarct 2-8 weeks: grey-white scar
Describe the macroscopic (gross) changes in MI with time.
- Pink amorphous tissue referred to as hyaline - Hyperplastic smooth muscle with an onion ring appearance seen mainly in hypertension
What is the wall thickened by in arteriosclerosis?
In the sub endothelial area and extends towards the pericardium over 3-6 hours. Subendothlial area is the furthest away from the supply vessels and subject to intralumnial pressure.
Where does necrosis begin and why?
Pooling of blood in the lungs (pulmonary oedema)
What is the result of left ventricular heart failure?
Block beta1 and beta2 receptors from adrenaline and noradrenaline. Decreases heart rate and dilates vessels reducing the heart rate. E.g. Atenalol, Metoprolol.
Why are Beta-blockers used? Give two drug examples.
20 minutes.
How long must myocardium be ischaemic for necrosis to occur?
Media is thinned with loss of staining underlying an atherosclerotic plaque. The plaque has a necrotic centre containing cholesterol clefts and calcification. There is an overlying fibrous cap.
Describe the pathological features of this section of aorta.
Ulcerated plaques are present along aorta. A small aneurysm in the lower aorta with a thrombus present within it. A similar finding is noted in the right and left iliac arteries.
Describe the pathological features of this section of aorta.
- Beta-blockers - ACEi/ARBs/Aldosterone inhibitors - Diuretics
What is the pharmacological treatment of heart failure?
Damaged muscle will leak enzymes, the rise in the blood proportional to the amount of damage. Traditionally measured: - Creatine kinase - Lactate dehydrogenase - Aspartate transaminase Currently measured: - Creatine kinase (begins to rise after 6-9 hours and rapidly cleared) - Troponin - T & I (cTnT and cTnTI)
Describe the cardiac enzyme changes characteristic of myocardial infarction.
Rupture of the fibrous cap with bleeding into the plaque narrowing the lumen which is occluded by an overlying thrombus.
Describe the pathology in this image.
Inhibit the angiotensin II receptor. Results in perivascular muscle relaxation and a drop in blood pressure. E.g. Losartan, Valsartin.
Why are angiotensin receptor blockers used? Give two drug examples.
Above the bifurcation bellow the renal arteries.
Where are aortic aneurysm usually found?
Takes years to develop as the scar tissue slowly weakens and allows the involved area to dilate.
How does myocardial infarction result in ventricular aneurysm?
Loss of elastin and the thinning of the media. Residual atherosclerotic debris represents the intima and thrombus is above this. Grossly thrombus would fill the cavity of aneurysm.
Describe the histology of this section from the base wall of an aortic aneurysm (elastin stained black, fibrous tissue is red).
Transverse section through abdomen and aortic aneurysm, aorta very enlarged with wall calcification, large darker mural thrombus within this with a small lumen containing flowing blood.
What is seen in this image?
3-7 days post-MI. - Septal, free wall → cardiac tamponade - Papillary muscle → acute valve dysfunction
How long after a MI is myocardial rupture likely to happen and what are the two types?
Peripheral oedema, raised JVP and liver congestion.
What are the consequences of increased pressure on the right ventricle?
Well done :D :D
This image is a helpful diagram of the last flashcard :D
Transmural
In which distribution of myocardial infarction is development of pericarditis most common?
- Rise rapidly in 2-3 hours - Remain raised for 4-10 days - Very specific and sensitive - Raised in many other conditions affecting the heart
Select the correct properties of troponin enzyme testing: - Rise rapidly in 2-3 hours or rise slowly in 10-12 hours - Cleared quickly in 24 hours or remain raised for 4-10 days - Not very specific and sensitive or very specific and sensitive - Raised in many other conditions affecting the heart or raised only in MI
Compression of the heart by an accumulation of fluid in the pericardial sac.
What is cardiac tamponade?
Inhibits angiotensin converting enzyme. Causes relaxation of blood vessels and decreases blood volume this decreasing blood pressure. E.g. Enalapril, Captopril.
Why are ACE inhibitors used? Give two drug examples.
Due to left ventricular failure (>20% damage to LV mass) or cardiogenic shock (>40% damage to LV mass).
How does myocardial infarction result in heart failure?
Discrete area of coagulative necrosis in myocardium. Due to ischaemia as the result of significant obstruction or total occlusion of a coronary artery.
What is myocardial infarction?
Uncomplicated atherosclerotic plaque at top. Dilation of the lower aspect of the aorta bellow the renal arteries forming an aneurysm. Aneurysm contains a large thrombus (red/brown area). Haemorrhage in periaortic fat (left) indicates aortic rupture.
Describe the pathological features of this section taken from an aortic aneurysm.
Increased pressure (right ventricle pumps blood into pulmonary circuit).
What affect does pulmonary oedema have on the right ventricle?
Coughing, frothy sputum, shortness of breath, orthopnoea, paroxysmal nocturnal dyspnoea and crepitations
What are the consequences of pulmonary oedema?
- Lumen narrowed by 70% - Intima eccentrically thickened - Atherosclerotic plaque
Describe the pathological features of this section of artery.
Cardiac function decreased due to loss of functioning muscle.
What is heart failure?
- Subendothelial: inner area of myocardium does not receive adequate oxygen - Mural: deep within the muscle but not full thickness - Transmural: full thickness except for a small rim of viable tissue in the sub endothelial and supercardial areas
What are the three distributions a MI can have?
- Arrhythmias - Heart failure - Mural thrombus - Pericarditis - Myocardial rupture - Ventricular aneurysm
What are 6 possible complications of myocardial infarction?
Right side of vessel is large atherosclerotic plaque into which there has been a hemorrhage. Cholesterol clefts and calcification are seen. The fibrous cap shows a rupture and the lumen has been significantly narrowed by an occlusive thrombus. Vessel can be seen in the shoulder of the fibrous cap on the left.
Describe the pathology of this section of atherosclerotic artery.
Thinning of muscular media and loss of elastic fibres of the internal and external laminae. Intima eccentrically thickened by atherosclerotis plaques. Plaque is necrotic and contain cholesterol clefts. Overlying fibrous cap present. Small bleed inferiorly from the vessels of the shoulder of the fibrous cap.
Describe the pathological features of this section of artery.
Due to enhanced sympathetic activity as a result of increased levels of local or circulating catecholamines.
How do myocardial infarction result in arrhythmias?
A - mild atherosclerosis with fibrous plaques as indicated by the arrow B - Severe atherosclerosis with complicated plaques which are ulcerated with overlying thrombi. These may be a source of emboli.
Describe the pathology seen in these images of separate aorta.
VGE stain - elastic tissue is black and collagen red. Atherosclerotic plaque seen on top. Media with some disruption of elastin (black area).
Describe the pathological features of this aortic section not involved with the aneurysm.
- Large overlying plaque impedes O2 from nourishing the inner aspect of the media - Weakening of the media with loss of smooth muscle - Wall bulges forming a dip on the lumen aspect - Turbulent blood flow through dip results in thrombus formation - Further thinning and weakening and further thrombus formation establish the aneurysm
Order these events chronologically in the pathogenesis of atherosclerotic aneurysm: - Weakening of the media with loss of smooth muscle - Further thinning and weakening and further thrombus formation established the aneurysm - Turbulent blood flow through dip results in thrombus formation - Large overlying plaque impedes O2 from nourishing the inner aspect of the media - Wall bulges forming a dip on the lumen aspect
- Presentation as an abdominal mass - Source of distal emboli - Rupture into the abdominal cavity - Occlusion of branch vessels of the aorta
What complications can result from aortic aneurysms?
- Onset of intense crushing chest pain - May radiate to the jaw and left arm - Sweating, nausea and vomiting
Describe the clinical symptoms of myocardial infarction.
Well done :D :D
This image is a helpful diagram of the last flashcard :D
- Dead muscle does not conduct electrical impulses and this can be detected with the ECG - Typically ST elevation in leads associated with the area of myocardial damage is seen
Describe the ECG changes characteristic of myocardial infarction.
Section 8
(50 cards)
• Results from a cycle of obstruction/infection → damage to airways → healing by fibrosis → dilation →accumulation of mucus → obstruction/infection. • With continual inflammation and fibrosis, the small airways may become obstructed by fibrosis.
What causes bronchiectasis and what does it lead to?
Focus of inflammation in lung is around airways.
What is meant by bronchocentric inflammation?
The permanent dilation of bronchi and bronchioles.
What is bronchiectasis?
• Metaplasia of the normal respiratory epithelium to squamous epithelium • Hyperbolas of the mucus components of the bronchial glands with loss of serous glands • Basement membrane thickened • Smooth muscle is hypertrophied due to constant coughing.
Describe the histology of the chronic bronchitis in this section of bronchi wall.
Viable fibres at the top of the image. Dead fibers at the bottom, have no nuclei, loss of striations, decreased in size and surrounded by neutrophils.
Describe the histology of this image:
• Local/diffuse • External compression
What are the two types of airway obstruction?
• Goblet cell hyperplasia • Infiltrates of neutrophils, macrophages and T and B cells • Thickening of bronchiole walls due to peribronchiolar fibrosis and muscle hypertrophy
Describe the inflammatory effects of smoking in young people.
Centrilubular (acinar)
What type of emphysema is shown in this image?
• Hairs • Turbinates • Mucosal lysosomes and immunoglobulins (IgA)
What immunological defences are found in the nose?
Common, noncancerous, teardrop-shaped growths that form in the nose or sinuses.
What are nasal polyps?
• The dilated airways contain mucus plugs (white regular circular outline). • Irregular pink areas surrounding the airways are foci of pneumonia - the infection has spread to the parenchyma from the airway.
Describe this image of lungs with bronchiectasis from a patient with cystic fibrosis.
Mural thrombus.
What pathological process is featured in this image?
Spiral shaped mucus plugs that may contain desquamated epithelium that may be seen in the airways of some asthmatics.
What is a Curschmann's spiral?
• Obstruction of the lumen (foreign body, intraluminal tumour, mucus, increased thickness of the wall) • Fibrosis of the bronchial wall (result of damage to the wall followed by healing)
Describe local/diffusion obstruction.
Protect from aspiration.
What is the purpose of the glottic and cough reflexes?
Green - goblet cell hyperplasia Blue - thickened basement membrane Yellow - eosinophil infiltration Red - muscle hypertrophy
Describe the points indicated by shapes in this bronchiole of an asthmatic.
Inflammatory mediators from epithelial cells, alveolar macrophage and migrated leucocytes, especially, proteases (elastase) and oxidative species.
What is the cause of alveolar wall destruction in emphysema?
Act as a diuretic but have the benefit of sparing potassium loss. E.g. Spironolactone.
Why are aldosterone antagonists used? Give a drug example.
Panacinar
What type of emphysema is shown in this image?
Increase urine output decreasing blood volume. E.g. thiazide family of diuretics are the most commonly used.
Why are diuretics used? Give a drug example.
• Childhood onset • May be preceded by eczema • Commonly associated with rhinitis • Generally responds well to treatment • Specific IgE testing positive • Most common allergens indoor
What is allergic asthma?
An inherited autosomal recessive monogenic disorder presenting as a multisystem disease.
What is cystic fibrosis?
• Centrilobular (acinar) • Panacinar
What are the two types of emphysema?
• Early phase response - Type I hypersensitivity - IgE antibody with mast cells • Late phase response - Type IV hypersensitivity - T cell mediated response activates eosinophils, B cells, others
Describe the early and late phase response of airway inflammation.
• Goblet cell hyperplasia • Macrophage accumulation with destruction of elastic tissue • Fibrosis around bronchioles • May result in obliteration of the bronchiole
Describe the histology of the chronic bronchitis in this section of small airway wall.
1. Airway inflammation 2. Bronchial hyper-responsiveness 3. Bronchoconstriction 4. Bronchial wall oedema 5. Excess mucus secretion 6. Epithelial shedding 7. Airway remodelling
Describe the pathophysiology of asthma.
Mucociliary stream - removes particles from inhaled air and moves them up to the pharynx to be swallowed.
What immunological defences are found in the major airways?
Macrophages phagocytose foreign particles and microorganisms.
What immunological defences are found in the alveolar?
Obstruction of the airway as a result of tumour.
Describe external compression obstruction?
• Mucus hyper secretion • Airway oedema • Fibrosis of the bronchiolar walls • Bronchoconstriction
How does persistent inflammation from smoke exposure lead to small airways disease in chronic bronchitis?
Leads to loss of elastic recoil with collapse of the airways during expiration (pursed lip breathing).
What effect does alveolar wall break down have during expiration?
A condition of reversible airways obstruction.
What is asthma?
Rupture of free wall of ventricle
What pathological process is featured in this image?
The destruction of the alveolar walls distal to the terminal bronchiole resulting in irreversible enlargement of the airspaces. Fibrosis is not obvious. Smaller airways fibrosis contributes to obstruction.
What is emphysema?
Chest is hyper-inflated: • Diaphragms are flat • Lung markings reduced • Expansion of lung tissue in the apices • Ribs are parallel in orientation • Heart shadow is narrowed
Describe the appearance of this emphysema chest x-ray.
Unable to move chloride ions out of a cell causing sticky mucus to build up on the outside of the cell.
Describe the effect of the cystic fibrosis mutation on the CFTR channel.
Cough productive of sputum on most days for 3 months of at least 2 successive years. An epidemiological definition. Does not imply airway inflammation.
What is chronic bronchitis?
Often bilateral basal patchy opacification, relating to the focal nature of the consolidation.
Describe the common pattern observed for bronchopneumonia on a CXR.
Ventricular aneurysm, formed due to stretching and expansion of an old area of scarring in the myocardium. It may rupture.
Describe the pathology of this image.
• Mucus plugging lumen • Hyperplasia of smooth muscle • Thickened basement membrane
Describe the pathology of this section of bronchus from asthma death.
Ruptured papillary muscle
What pathological process is featured in this image?
Centrilobular affects the respiratory bronchioles, while panacinar emphysema affects the alveoli and alveolar ducts.
What is the difference between centrilobular (acinar) and panacinar emphysema?
• Late onset (adulthood) • Allergy tests negative • Commonly associated with sinusitis and nasal polyps • Responds less well to treatment • Needs higher doses of steroids to control
What is intrinsic asthma?
Sammich.
Diffuse obstructive airway disease has something to do with small airway disease e.g. emphysema, chronic bronchitis, asthma.
Acinus (respiratory bronchiole, alveolar ducts and alveoli): • Loss of elastic recoil • Gas exchange becomes difficult → air becomes trapped
Describe the effects of emphysema?
Yay :)
Look a model of everything you just read!
• Loss of airflow and collapse of dependent lung as gases reabsorbed into circulation • Mucus drainage ceases and macrophages ingest 'this material' and remain in local area resulting in lipoid pneumonia • If the obstruction is chronic infection may follow eventually leading to bronchiectasis.
Describe the effects of localised obstruction.
• Allergy • Infection • Cold • Exertion • Irritation • Drugs • Occupation exposure • Exercise
Give some examples of asthma triggers.
• Smoking • Atmospheric pollution • Genetic factors
What are the risk factors of COPD?
• Chemokines and cytokines maintain myofibroblasts in an activated state • Activated myofibroblasts produce increased levels of matrix protein leading to airway wall thickening • Activated myofibroblasts are also involved in increasing smooth muscle mass leading to lumen reduction
Describe the causes of airway remodelling.
Section 9
(29 cards)