Stem Cells and Tissue Repair Quiz

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Questions and Answers

What is a key characteristic of stem cells?

Permanent presence in all tissues

Ability to undergo symmetric replication

Limited differentiating potential

Self-renewal capacity (correct)

Which factor is considered systemic in influencing tissue repair?

Local infection

Mechanical factors

Angiogenesis

Nutrition, such as vitamin C (correct)

What role do growth factors play in tissue repair?

They inhibit macrophage activity

They drive cell proliferation (correct)

They enhance blood supply directly

They replace damaged DNA

In which stage of scar formation does deposition of ECM proteins occur?

Scar formation Signup and view all the answers

Which type of stem cell has pluripotent characteristics?

Embryonic stem cells Signup and view all the answers

What is the main function of the extracellular matrix (ECM)?

Mechanical support and tissue microenvironment establishment Signup and view all the answers

How does glucocorticoids impact tissue repair?

Inhibit TGF-β production and fibrosis Signup and view all the answers

Which process involves the degradation of the extracellular matrix to facilitate angiogenesis?

MMP activity Signup and view all the answers

What is a characteristic feature of amyloid deposits as seen under electron microscopy?

Non-branching, constant diameter of 8-10 nm Signup and view all the answers

Which immunohistochemical finding can help distinguish between different types of amyloidosis?

Antibodies targeting AA and AL proteins Signup and view all the answers

What is the pathogenesis linked to AL amyloidosis?

Overproduction of light chains of immunoglobulins Signup and view all the answers

Which staining method would reveal the characteristic apple green birefringence associated with amyloidosis?

Congo red Signup and view all the answers

Which type of amyloidosis is most commonly associated with chronic inflammation?

AA amyloidosis Signup and view all the answers

What type of protein is associated with Aβ amyloidosis, which is notably found in Alzheimer's disease?

Amyloid precursor protein Signup and view all the answers

What is the primary cause of renal failure in patients with light chain deposition disease (LCDD)?

Defective proteolysis and accumulation of light chains Signup and view all the answers

Which common site for biopsy is used to establish a diagnosis of amyloidosis?

Rectum Signup and view all the answers

Which type of carcinoma is known for not metastasizing despite its invasive nature?

Basal cell carcinoma Signup and view all the answers

What does the grading of a tumor primarily indicate?

The rate of tumor cell proliferation Signup and view all the answers

Which of the following describes a systemic effect of a tumor?

Caching leading to progressive weight loss and immunocompromised state Signup and view all the answers

What distinguishes squamous cell carcinoma from adenocarcinoma in terms of architecture?

Presence of keratin pearls Signup and view all the answers

What characterizes dysplasia in epithelial tissues?

Disordered growth potentially reversible Signup and view all the answers

Which paraneoplastic syndrome is associated with lung cancer and manifestations like clubbing?

Hypertrophic osteoarthropathy Signup and view all the answers

Which metabolic change is primarily responsible for cancer cachexia?

Increased metabolism with raised inflammation Signup and view all the answers

What is a common clinical example of a local effect of a tumor?

Bowel obstruction Signup and view all the answers

Which of the following features is common in adenocarcinoma?

Mucin secretion Signup and view all the answers

What type of hormone-related paraneoplastic syndrome is associated with lung cancer?

Ectopic ACTH secretion Signup and view all the answers

What is the common location for gastric ulcers?

Lesser curvature Signup and view all the answers

Which type of gastric cancer has the worst prognosis?

Diffuse type Signup and view all the answers

Which of the following complications is associated with duodenal ulcers?

Perforation Signup and view all the answers

What percentage of ulcer cases is accounted for by gastric ulcers?

25% Signup and view all the answers

Which risk factor is specifically associated with gastric adenocarcinoma?

Helicobacter pylori infection Signup and view all the answers

Which type of gastric polyp is classified as non-neoplastic?

Fundic gland polyp Signup and view all the answers

Which classification describes the characteristics of gastric adenocarcinoma?

Intestinal type with cohesive mucin Signup and view all the answers

What histological feature is associated with the diffuse type of gastric cancer?

Signet ring cells Signup and view all the answers

Which of the following is a characteristic of the Borrmann classification type 3 gastric tumor?

Ulcerated with poorly defined margins Signup and view all the answers

Which condition is linked to Zollinger-Ellison syndrome?

Gastrin tumor Signup and view all the answers

What is the primary characteristic of a venous thrombus?

RBC-rich and fibrin-rich Signup and view all the answers

Which of the following describes 'embolism'?

A detached mass that travels to a distant site Signup and view all the answers

What is the most common clinical manifestation of fat embolism?

Pulmonary edema Signup and view all the answers

In which clinical condition does disseminated intravascular coagulation (DIC) most commonly occur?

Sepsis Signup and view all the answers

Which type of shock is primarily due to inadequate circulating blood volume?

Hypovolemic Signup and view all the answers

What is the mechanism behind transudate formation in oedema?

Increase in hydrostatic pressure Signup and view all the answers

Which of the following complications may arise as a consequence of shock?

Acute tubular necrosis in kidneys Signup and view all the answers

What type of embolism is most commonly associated with amniotic fluid?

Amniotic fluid embolism Signup and view all the answers

Identify the primary difference between transudate and exudate.

Exudate has a high protein concentration. Signup and view all the answers

What outcome may result from the propagation of a thrombus?

Increased risk of occlusion. Signup and view all the answers

What primary pathophysiological change occurs in the liver during congestive heart failure?

Nutmeg appearance of the liver. Signup and view all the answers

Which factor does NOT lead to edema formation?

Increased red blood cell count. Signup and view all the answers

Which type of shock typically results from an allergic reaction?

Anaphylactic shock Signup and view all the answers

Which of these is a common clinical presentation associated with amniotic fluid embolism?

Cyanosis Signup and view all the answers

Study Notes

Tissue Repair

Permanent tissue cannot be replaced after damage and is repaired by scar formation.
Stem cells have the capacity for self-renewal and asymmetric replication.
- Embryonic stem cells are pluripotent and originate from the inner cell mass.
- Adult stem cells are found within organs and tissues, have limited self-renewal, and differentiate potential.
Growth factors are polypeptides that drive cell proliferation and act in autocrine, paracrine, or endocrine manners.
- Main source: macrophages, lymphocytes, and stromal cells.
Extracellular matrix consists of basement membrane and interstitial matrix.
- Damaged ECM can only be repaired by scar formation.
- Functions: mechanical support for cell anchorage and migration, control cell proliferation, scaffold for tissue renewal, and establishes tissue microenvironment.
Scar formation occurs in severe and chronic tissue injury or damage in non-dividing cells.
- Steps:
  - Removal of destroyed tissue by phagocytosis.
  - Granulation tissue: angiogenesis and migration of fibroblasts.
    - Angiogenesis is driven by VEGF, FGF, and MMPs which degrade ECM to allow for blood vessel formation.
  - Scar formation: deposition of ECM proteins by fibroblasts with the aid of TGF-β, PDGF, and FGF.
  - Connective tissue remodelling with the use of MMPs.
Factors influencing tissue repair:
- Systemic Factors:
  - Nutrition: Vitamin C is essential for collagen synthesis.
  - Metabolic status: Diabetes significantly impairs wound healing.
  - Blood supply: Atherosclerosis can hinder blood flow to the wound site.
  - Glucocorticoids: Inhibit TGF-β production and fibrosis.
- Local Factors:
  - Infection: Delays healing and increases scar formation.
  - Mechanical factors: Chronic irritation or pressure can impede wound healing.

Tumour

Basal cell carcinoma (BCC) invades but does not metastasize.
Staging determines the extent of tumor spread and prognosis, using the TNM (tumor, nodes, metastasis) system.
Grading assesses the tumor's growth rate and aggressiveness. Higher grade tumors usually have a lesser degree of differentiation.
Standard description of tumor:
- Squamous cell carcinoma: Characterized by squamous differentiation.
  - Architecture:
    - Proliferation of tumor cells with squamous differentiation.
    - Arranged in nests and sheets with keratin pearls.
  - Cytology:
    - Malignant cytology with nuclear pleomorphism, hyperchromasia, enlargement, increased nuclear-to-cytoplasmic ratio, and frequent mitosis.
    - Intercellular bridges.
- Adenocarcinoma: Characterized by glandular differentiation.
  - Architecture:
    - Proliferation of tumor cells with glandular differentiation.
    - Arranged in infiltrative irregular and complex glands.
  - Cytology:
    - Malignant cytology with nuclear pleomorphism, hyperchromasia, enlargement, increased nuclear-to-cytoplasmic ratio, and frequent mitosis.
    - Mucin secretion.

Clinical Effects of Tumor

Local effects:
- Mass effect (SOL): Compression and impingement of surrounding structures.
  - Example: Brain tumor can cause midline shift and herniation.
- Blocking lumen: Obstruction of the hollow organ lumen.
  - Example: Bowel tumor causing intestinal obstruction.
- Ulceration and bleeding: Damage to the lining of the organ.
  - Example: Stomach tumor causing gastrointestinal bleeding.
- Invasion: Spread of tumor cells into adjacent tissues and organs.
  - Example: Lung tumor infiltrating the ribs.
- Rupture/infarct: Breakdown or blockage of blood supply.
  - Example: Liver tumor rupture.
- Secondary infection: Bacterial invasion due to compromised immune system.
  - Example: Biliary infection due to biliary stasis.
Systemic effects:
- Cachexia: Progressive weight loss, anorexia, anemia, and immunosuppression.
  - Pathogenesis: Increased metabolism, inflammation, and elevated pro-inflammatory cytokines.
- Paraneoplastic syndromes: Non-metastatic systemic effects related to tumor production of hormones or other substances.
  - Endocrine paraneoplastic syndromes:
    - Hypercalcemia of malignancy:
      - Caused by: Production of parathyroid hormone-related protein (PTHrP) or prostaglandins (PGs).
      - Typical tumor types: Head and neck squamous cell carcinoma (HNSCC), lung cancer, and renal cell carcinoma (RCC).
    - Syndrome of inappropriate antidiuretic hormone (SIADH):
      - Caused by: Production of antidiuretic hormone (ADH) or ADH-like hormone.
      - Typical tumor types: Lung cancer.
    - Cushing's syndrome:
      - Caused by: Production of adrenocorticotropic hormone (ACTH).
      - Typical tumor types: Lung cancer.
  - Hypertrophic osteoarthropathy (HOA):
    - Clubbing, periosteal bone formation, and arthritis.
    - Commonly seen in lung cancer.
  - Neurological paraneoplastic syndromes:
    - Myasthenic syndrome, peripheral neuropathy, polymyopathy, and cortical cerebellar degeneration.
  - Vascular phenomenon:
  - Fever: Most common presenting symptom.
  - Nephrotic syndrome:

Dysplasia

Disordered growth and maturation of an epithelium, potentially reversible.
Pre-invasive neoplastic process without stromal invasion.

Thrombus

Arterial thrombus (white): Platelet-rich, fibrin-poor.
Venous Thrombus (red): RBC-rich, platelet-poor, fibrin-rich.
Fate of the thrombus:
- Dissolution: Newly formed thrombi shrink by activation of fibrinolytic factors. Old thrombi are more resistant.
- Organization: Thrombi are invaded by fibroblasts and endothelial cells, forming new and smaller conduits.
  - Recanalization: Incorporated into the vessel wall.
  - Digestion: Central portion of the thrombus is digested by enzymes from trapped macrophages. This can serve as a culture medium for bacteria, weakening the vessel wall and leading to mycotic aneurysm.
- Propagation: Enlargement of the thrombus by obtaining additional platelets and fibrin, increasing the risk of occlusion.
- Embolism: Thrombus dislodges and travels to a distant site in the vasculature, causing obstruction.

Embolism

Detached mass (solid, liquid, or gas) transported through the bloodstream to a distant site.
- Thromboembolism:
  - Pulmonary embolism: Most commonly from deep vein thrombosis (venous)
  - Systemic embolism: Most commonly from the heart, leading to tissue infarct.
- Fat embolism:
  - Source: Fractured long bones, fatty liver.
  - Marrow fat enters ruptured marrow sinusoids and travels to pulmonary capillaries, then embolised to the brain, kidneys, etc.
  - Presentation: Dyspnea, tachycardia, renal failure, delirium, and coma.
  - Pathology: Revealed by oil red O stain.
- Amniotic fluid embolism:
  - Source: Tears in the placental membrane and/or uterine vessels.
  - Presentation: Cardiopulmonary collapse + DIC.
  - Presentation: Dyspnea, bleeding (due to DIC).
  - High mortality; survivors may have neurological impairment.
- Air embolism:
  - Source: Rapid ascent in scuba diving.
  - Presentation: "Bends" (severe pain in joints and bones), pulmonary edema, bleeding atelectasis.
- Paradoxical emboli:
  - Source: Venous emboli passing through a patent foramen ovale (PFO) or ventricular septal defect (VSD) into the systemic circulation.

Disseminated Intravascular Coagulation (DIC)

Thrombohemorrhagic disorder causing ischemic damage (fibrin thrombi block the microcirculation) and bleeding from the gastrointestinal tract, nose, and puncture sites.
Pathogenesis:
- Consumption coagulopathy:
  - Widespread intravascular deposition of fibrin, leading to decreased platelet and schistocytes.
  - Consumption of platelets and clotting factors resulting in prolonged aPTT, PT, TT, and decreased fibrinogen.
- Activation of fibrinolysis: Increased fibrin degradation products (FDPs) and D-dimer.
DIC-associated clinical disorders:
- Obstetric: Amniotic fluid embolism, eclampsia.
- Infections: Gram-negative sepsis (most common).
- Neoplasm: Acute promyelocytic leukemia, adenocarcinoma.
- Massive tissue injury: Trauma, burns.
- Others: Snake venom, shock.

Oedema

Increased accumulation of fluid in the interstitial space of the extracellular fluid compartment.
Pathophysiology:
- Increased hydrostatic pressure:
  - Example: Congestive heart failure (CHF) due to increased central venous pressure (CVP) and water/sodium retention.
  - Other examples: Constrictive pericarditis, venous obstruction, liver cirrhosis (portal hypertension).
- Decreased oncotic pressure:
  - Example: Nephrotic syndrome due to decreased albumin production.
  - Other examples: Malnutrition, protein-losing enteropathy, and liver cirrhosis.
- Lymphatic obstruction:
  - Example: Inflammatory breast cancer due to lymphatic blockage by malignant cells.
  - Other examples: Lymphoedema after radical mastectomy.
- Increased capillary permeability:
  - Example: Toxins causing direct damage to the endothelium.
  - Chemical mediators causing retraction of endothelial cells.
Types of oedema:
- Transudate: Shift in Starling forces (hydrostatic/oncotic).
  - Low protein content, absent fibrinogen, few cells, dependent pitting edema, and obeys the law of gravity.
- Exudate: Increased permeability.
  - High protein content, present fibrinogen, inflammatory cells, non-pitting edema due to increased viscosity caused by high protein and cell content.

Congestion and Hyperaemia

Hyperaemia: Increased blood volume within a tissue.
- Active process: Arteriolar dilation and increased inflow.
- Red (erythema): Reflects increased blood flow.
Congestion: Impaired outflow, passive vasodilation.
- Blue-red (cyanosis): Reflects poor blood flow.
Morphology:
- Liver congestion (nutmeg appearance): Centrilobular zone necrosis (red/brown) surrounded by uncongested periportal zone (tan-colored).
- Pulmonary congestion: Engorged alveolar capillaries.

Shock

Systemic hypoperfusion due to reduced effective circulating blood volume (ECV).
Types of shock:
- Cardiogenic shock:
  - Examples: Myocardial infarction, pulmonary embolism, cardiac tamponade, arrhythmia.
  - Mechanisms: Pump failure, obstruction to outflow, extrinsic pressure.
- Hypovolemic shock:
  - Examples: Haemorrhage, fluid loss.
  - Mechanisms: Inadequate blood volume.
- Septic shock:
  - Examples: Bacteremia.
  - Mechanisms: Gram-positive (LTA) or gram-negative (LPS, endotoxin).
- Neurogenic shock:
  - Examples: Anesthesia, spinal injury.
  - Mechanisms: Loss of vascular tone.
- Anaphylactic shock:
  - Examples: Allergy.
  - Mechanisms: IgE-mediated hypersensitivity reaction, complement activation, histamine release.
Presentations:
- Vasodilation: Hypotension, weak pulse, cold clammy skin.
- Low cardiac output: Tachycardia, oliguria, mental changes.
- Acute respiratory distress syndrome (ARDS): Hyperventilation, pallor/cyanosis.
- Disseminated intravascular coagulation (DIC): Haemorrhage.
Stages:
- Non-progressive: Perfusion maintained by neurohumoral compensatory mechanisms.
- Progressive: Widespread tissue hypoxia affecting vital organs.
- Irreversible: Widespread cell injury leading to inevitable death.
Consequences:
- Brain, heart: Irreversible damage.
- Kidneys: Acute tubular necrosis.
- Lungs: Diffuse alveolar damage (shock lung).
- Adrenals: Lipid depletion due to increased utilization for steroid synthesis.
- GIT: Mucosal ulcerations, hemorrhages.
- Liver: Fatty changes, perivenular necrosis.
Prognosis:
- Best for hypovolemic and neurogenic shock.
- Worst for cardiogenic (no compensatory mechanisms) and septic (difficult to gauge cytokine release and DIC).

Amyloidosis

Deposition of fibrillar protein in extracellular interstitial tissue, leading to organ dysfunction via pressure atrophy.
Morphology:
- Electron microscopy (EM): Linear, non-branching fibrils with 8-10 nm diameter and varying lengths.
- X-ray crystallography: Beta-pleated sheet arrangement.
Tissue diagnosis:
- Tissues biopsied: Rectum, gingiva, omental fat pad.
- H&E: Amorphous eosinophilic hyaline between cells.
- Congo red stain: Orange-red to pink/red.
- Polarizing microscopy: Apple-green birefringence.
- Immunohistochemistry: Differentiation between AA, AL, and Aβ.
- EM: Differentiate amyloidosis from other fibrillary diseases.
Biochemical forms and pathogenesis:
- AL (amyloid light protein):
  - Origin: Light chains of immunoglobulin (gamma > kappa).
  - Pathogenesis: Plasma cell dyscrasia, leading to increased immunoglobulin or Bence Jones protein production, defective proteolysis, or protein misfolding.
  - Remarks: Amyloidosis or non-amyloidosis condition (renal cast nephropathy, light chain deposition disease (LCDD) → renal failure).
- AA (amyloid-associated fibril):
  - Origin: Serum amyloid-associated protein (SAA).
  - Pathogenesis: Chronic inflammation, leading to increased IL-1/6 production, sustained increased SAA from the liver, defective proteolysis, or protein misfolding.
  - Remarks: Most common type worldwide.
- Aβ:
  - Origin: Amyloid precursor protein (APP).
  - Found in Alzheimer's disease.
- Other possible proteins:
  - ATTR (transthyretin): Carrier protein for thyroid hormone (T4) and vitamin A.
  - Zollinger-Ellison syndrome (gastrin tumour): Multiple ulcers.

Peptic Ulcer Disease

Meckel diverticulum:
- Zollinger-Ellison syndrome (gastrin tumour): Multiple ulcers.

Gastric Neoplasms

Gastric polyps:
- Non-neoplastic (>90%):
  - Hyperplastic/ inflammatory polyps: Associated with chronic inflammation.
  - Fundic gland polyps: Decreased acid production, leading to increased gastrin production and glandular hyperplasia.
- Neoplastic:
  - Gastric adenoma: Risk of adenocarcinoma, related to size.
Malignant neoplasms:
- Carcinoma: 85-90%
- Lymphoma: 5-10%
- Mesenchymal tumor (GI stromal tumor): 2%
- Carcinoid tumor: 0.3%

Gastric Adenocarcinoma

Decreased incidence, but higher in Asia.
Locations: Lesser curvature and antrum (most common) > cardia.
Risk factors:
- Environment: Smoking, smoked food, diet (nitrosamines), pernicious anemia, gastric adenoma.
- Host: Helicobacter pylori (HP), Epstein-Barr virus (EBV).
- Genetics: APC, Lynch syndrome, hereditary diffuse gastric cancer syndrome (HDGC), blood group A.
Gross classification (Borrmann):
- Type 1: Polypoid.
- Type 2: Fungating with sharp raised margins.
- Type 3: Ulcerated with poorly defined margins.
- Type 4 (linitis plastica): Diffuse infiltration due to desmoplastic reaction stiffening the gastric wall.
Microscopic classification (Lauren):
- Intestinal type (MC):
 - Associated with: Most environmental risk factors, but no family history.
 - Histological features: Cohesive, gland formation, mucin secretion.
 - HER2 amplification: 10-15%
 - Prognosis: Better.
- Diffuse type:
 - Associated with: Hereditary diffuse gastric cancer syndrome (HDGC) (E-cadherin mutation).
 - Histological features: Discohesive mucinous cells, signet ring cells, linitis plastica.
 - HER2 amplification: < 1%
 - Prognosis: Worse.

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Test your knowledge on the essential characteristics of stem cells and the critical factors influencing tissue repair. This quiz covers topics such as growth factors, ECM roles, and the impacts of glucocorticoids. Perfect for students in biology and medical fields.