Human Growth and Development
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What is the definition of tall stature in terms of standard deviation?

  • Height > 1.6 SD above target height (correct)
  • Height > 2 SD above target height (correct)
  • Height > 3 SD above target height
  • Height > 1 SD above target height

    • What is the most common chromosomal cause of short stature?

  • Noonan syndrome
  • Klinefelter syndrome
  • Down syndrome (correct)
  • Turner syndrome

    • What is the name of the syndrome characterized by short stature, development delay, and congenital cardiac anomaly?

  • Turner syndrome
  • Down syndrome
  • FGFR3 syndrome
  • Noonan syndrome (correct)

    • What is the name of the gene mutation that causes achondroplasia?

    <p>FGFR3</p> Signup and view all the answers

    What is the term for short stature caused by an unknown etiology?

    <p>Idiopathic short stature</p> Signup and view all the answers

    What is the name of the new drug that has an effect on growth and possibly spinal stenosis in achondroplasia?

    <p>Vosoritide</p> Signup and view all the answers

    What is the characteristic feature of skeletal dysplasia?

    <p>Disproportionate short stature</p> Signup and view all the answers

    What is a characteristic of osteosarcoma (OS)?

    <p>There is no benign precursor for OS.</p> Signup and view all the answers

    Which genes are involved in hereditary Paget's disease of bone?

    <p>SQSTM1 and TNFRSF11A</p> Signup and view all the answers

    What is the result of a p53 mutation in a cell?

    <p>The cell cycle stops until DNA repair occurs.</p> Signup and view all the answers

    What is the incidence of osteosarcoma in Li-Fraumeni syndrome?

    <p>40% before age 50</p> Signup and view all the answers

    What is the result of a conditional knockout for Rb1 and Tp53 in osteoblastic precursor cells?

    <p>The mice develop osteosarcoma.</p> Signup and view all the answers

    What is characteristic of Paget's disease of bone?

    <p>Increased bone resorption and formation.</p> Signup and view all the answers

    What is the percentage of children with germline mutations in a cancer-predisposing gene in pediatric cancer?

    <p>8.5%</p> Signup and view all the answers

    What is the association between Paget's disease of bone and osteosarcoma?

    <p>Paget's disease increases the risk of developing osteosarcoma.</p> Signup and view all the answers

    What is the role of TP53 and RB1 genes in osteosarcoma?

    <p>They are tumor suppressor genes that are often mutated in osteosarcoma.</p> Signup and view all the answers

    What is the type of tumors that occur in retinoblastoma?

    <p>Malignant tumors of the retina.</p> Signup and view all the answers

    What is the main effect of the vosoritide on the growth of children with achondroplasia?

    <p>Increases the growth rate by 1.5 cm per year</p> Signup and view all the answers

    What is the characteristic feature of Leri-Weill dyschondrosteosis?

    <p>Madelung deformity and short 4th metacarpal bone</p> Signup and view all the answers

    What is the function of osteoclasts in bone remodeling?

    <p>To resorb bone</p> Signup and view all the answers

    What is the primary site of occurrence of giant cell tumor of bone?

    <p>Epiphysis or metaphysis of long bones</p> Signup and view all the answers

    What is genetic instability?

    <p>When a cell has a mutation in a gene that is important for DNA protection.</p> Signup and view all the answers

    What is the main criterion for evaluating the response to chemotherapy in giant cell tumor of bone?

    <p>Percentage of necrosis</p> Signup and view all the answers

    What is a driver event?

    <p>A mutation that leads to cancer development.</p> Signup and view all the answers

    What is the mode of inheritance of Leri-Weill dyschondrosteosis?

    <p>Pseudo-autosomal</p> Signup and view all the answers

    What is the effect of vosoritide on blood pressure?

    <p>Decreases blood pressure</p> Signup and view all the answers

    What is the difference between inherited cancer and familial clustering?

    <p>Inherited cancer has a known genetic basis, while familial clustering does not.</p> Signup and view all the answers

    What is the characteristic feature of hyperachondroplasia?

    <p>Severe short stature</p> Signup and view all the answers

    What is a phenocopy?

    <p>A person who develops cancer but does not have a mutated gene.</p> Signup and view all the answers

    What is the role of osteoblasts in bone remodeling?

    <p>To form new bone</p> Signup and view all the answers

    What is retinoblastoma?

    <p>The first cancer for which genetic inheritance was elucidated.</p> Signup and view all the answers

    What is the percentage of risk of a baby having achondroplasia if one parent is affected?

    <p>50%</p> Signup and view all the answers

    What is the function of the shelterin complex?

    <p>It protects telomeres.</p> Signup and view all the answers

    What is the most common type of polyp that can lead to colon carcinoma?

    <p>Tubulovillous adenoma.</p> Signup and view all the answers

    What is the characteristic of hyperplastic polyp?

    <p>It has serrated lumina and no dysplasia.</p> Signup and view all the answers

    What is the difference between tubulovillous adenoma and tubular adenoma?

    <p>Tubulovillous adenoma has darker morphology, while tubular adenoma has lighter morphology.</p> Signup and view all the answers

    What is the characteristic feature of adenocarcinoma colon?

    <p>Submucosal proliferation of glands</p> Signup and view all the answers

    What is the name of the gene that is mutated in Familial Adenomatous Polyposis (FAP)?

    <p>APC</p> Signup and view all the answers

    What is the percentage of endometrial cancers in Lynch syndrome?

    <p>50%</p> Signup and view all the answers

    What is the name of the condition characterized by fibrotic scarring of glomeruli?

    <p>Glomerulosclerosis</p> Signup and view all the answers

    What is the name of the autosomal recessive polyposis syndrome caused by mutations in both alleles of the MUTYH gene?

    <p>MUTYH-associated polyposis</p> Signup and view all the answers

    What is the name of the type of glomerulosclerosis characterized by less than 50% of all glomeruli being involved with majority showing sclerosis?

    <p>Focal global glomerulosclerosis</p> Signup and view all the answers

    What is the name of the test used to screen for cancers in Lynch syndrome?

    <p>Colonoscopy</p> Signup and view all the answers

    What is the name of the gene that is often methylated in sporadic MSI-high CRC?

    <p>MLH-1</p> Signup and view all the answers

    What is the term used to describe the process of accumulation of mutations leading to colon carcinoma?

    <p>Stepwise process</p> Signup and view all the answers

    What is the percentage of the population that possesses a mutated copy of the MUTYH gene?

    <p>1-2%</p> Signup and view all the answers

    What is the result of granulocytes degranulating and producing proteases?

    <p>Creating holes in the wall, resulting in hemorrhage</p> Signup and view all the answers

    What is the characteristic of the immune complex in the sub-endothelial location?

    <p>Linear binding pattern with immunofluorescence</p> Signup and view all the answers

    What is the cause of sub-epithelial deposits?

    <p>Antibodies against epitopes in the sub-epithelial space</p> Signup and view all the answers

    What is the result of frustrated chemotaxis?

    <p>No inflammation and no symptoms for a long time</p> Signup and view all the answers

    What is the characteristic of membranous glomerulopathy?

    <p>Thickening of the basal membrane and spike-like structures</p> Signup and view all the answers

    What is the result of abnormal basal membrane production in membranous glomerulopathy?

    <p>Hyperproteinuria and edema</p> Signup and view all the answers

    What is the treatment for membranous glomerulopathy?

    <p>Protein-free diet and anti-inflammatory drugs</p> Signup and view all the answers

    What is the characteristic of the mesangial space?

    <p>Mesangial cells and mesangial matrix</p> Signup and view all the answers

    What is the cause of deposits in the mesangial space?

    <p>Circulating antibodies that are abnormal in their structure</p> Signup and view all the answers

    What is the result of deposits in the mesangial space?

    <p>Hematuria and nephritic syndrome</p> Signup and view all the answers

    What is the primary mechanism by which the immune response is slowed in IgA nephropathy?

    <p>The granulocytes cannot reach the immune complexes with their podia</p> Signup and view all the answers

    What is the characteristic of the basement membrane in diabetic nephropathy?

    <p>Thickening of the basement membrane</p> Signup and view all the answers

    What is the result of the loss of glycocalyx in diabetic nephropathy?

    <p>Pro-inflammatory and pro-thrombotic changes</p> Signup and view all the answers

    What is the role of VEGF in maintaining the microvasculature?

    <p>It is a positive regulator of vascular function</p> Signup and view all the answers

    What is the advantage of using animal models in diabetic nephropathy research?

    <p>They are fast to develop and genetically identical</p> Signup and view all the answers

    What is the effect of VEGF knockout on the glomerulus in diabetic mice?

    <p>It leads to an increase in extracellular matrix</p> Signup and view all the answers

    What is the role of podocytes in the production of VEGF?

    <p>They are one of the producers of VEGF</p> Signup and view all the answers

    What is the effect of streptozotocin on beta cells in the pancreas?

    <p>It inhibits the production of insulin</p> Signup and view all the answers

    What is the characteristic of the glomerulus in diabetic mice?

    <p>It is enlarged</p> Signup and view all the answers

    What is the effect of VEGF on the endothelial cells in the glomerulus?

    <p>It maintains the endothelial cells</p> Signup and view all the answers

    What is the primary mechanism by which alloantigens contribute to the formation of immune complexes in the kidney?

    <p>Alloantigens come from micro-organisms and are introduced to the bloodstream through infection.</p> Signup and view all the answers

    What is the result of granulocyte degranulation in the kidney?

    <p>The creation of literal holes in the capillary walls, leading to leakage of blood into the urine.</p> Signup and view all the answers

    What is the term for the syndrome characterized by hematuria, renal dysfunction, and hypertension?

    <p>Nephritic syndrome</p> Signup and view all the answers

    What is the primary location of immune complex deposition in the first type of glomerular localization?

    <p>Under the sub-endothelium</p> Signup and view all the answers

    What is the role of antibody in the formation of immune complexes in the kidney?

    <p>Antibodies bind to specific antigens, leading to the formation of immune complexes.</p> Signup and view all the answers

    What is the consequence of increased blood pressure in the kidney due to proliferation of cells?

    <p>Hypertension</p> Signup and view all the answers

    What is the term for the abnormal casts formed in the urine due to the presence of blood?

    <p>Erythrocyte cast</p> Signup and view all the answers

    What is the effect of VEGF inhibition in animal models of diabetic nephropathy?

    <p>Reduction of proteinuria</p> Signup and view all the answers

    What is the primary cause of glomerulosclerosis?

    <p>All of the above</p> Signup and view all the answers

    What is the location of the immune complex deposition in the second type of glomerular localization?

    <p>In the glomerular basal membrane</p> Signup and view all the answers

    What is the role of sFlt-1 in reducing renal complications in diabetic nephropathy?

    <p>Inhibiting VEGF-induced tube formation</p> Signup and view all the answers

    What is the role of granulocytes in the inflammatory response in the kidney?

    <p>To recognize and respond to immune complexes, leading to inflammation</p> Signup and view all the answers

    What is the primary function of the kidneys in regulating blood pressure?

    <p>Regulating blood pressure through fluid balance</p> Signup and view all the answers

    What is the characteristic feature of nephritic syndrome?

    <p>Presence of red blood cells in the urine</p> Signup and view all the answers

    What is the effect of VEGF-A on endothelial cells?

    <p>Inducing endothelial activation</p> Signup and view all the answers

    What is the role of M2 macrophages in the context of sFlt-1 treatment?

    <p>Binding to sFlt-1</p> Signup and view all the answers

    What is the characteristic feature of membranous nephropathy?

    <p>Immune complex deposition in the glomerulus</p> Signup and view all the answers

    What is the result of a mutation in the mismatch repair genes in Lynch syndrome?

    <p>Increased microsatellite instability</p> Signup and view all the answers

    What is the primary function of the kidneys in regulating electrolyte balance?

    <p>Regulating potassium levels</p> Signup and view all the answers

    What is the characteristic feature of acute renal insufficiency?

    <p>Sudden decline in renal function</p> Signup and view all the answers

    Study Notes

    Height and Stature

    • Height is 60-80% genetic, influenced by feeding, health, and medication
    • Low penetrance genes have a small influence on height, while high penetrance genes have a significant effect
    • Causes of short stature: • Primary growth disorder
      • Syndromes
      • Small for gestational age (SGA) without catch-up growth
      • Skeletal dysplasia
      • Disorder of bone metabolism • Secondary growth disorders
      • Malnutrition
      • Celiac disease
      • Hormonal disorder
      • Metabolic disorder • Idiopathic short stature (unknown cause)
    • Chromosomal causes of short stature: • Down syndrome • Turner syndrome (1 X chromosome or missing short arm of one X chromosome)

    Noonan Syndrome

    • Features: • Short stature • Development delay (mean IQ 86) • Facial features:
      • Broad neck
      • Low set ears
      • Hypertelorism, ptosis • Congenital cardiac anomaly • Pectus deformity • Lymphatic abnormalities • Coagulation defect • Cryptorchidism

    Skeletal Dysplasia

    • Abnormalities of epiphysis, metaphysis, and/or diaphysis
    • Causes disproportionate short stature (limbs too short for trunk or vice versa)
    • Examples: • Achondroplasia (Lili putian)
      • Features:
        • Short stature
        • Large head
        • Short arms and legs
        • Skin creases
        • Pronounced lumbar lordosis (bent back)
        • Deep nasal bridge
        • Frontal bossing (pronounced forehead)
        • Short hands with trident
      • Treatment: symptomatic, possibly Vosoritide (new drug with effect on growth and spinal stenosis) • Leri-Weill dyschondrosteosis
      • Features:
        • Short stature
        • Short arms and legs
        • Madelung deformity
        • Muscle hypertrophy
        • Short 4th metacarpal bone

    Disorders of Bone

    • HC/13 Giant cell tumour of bone: • Histology: giant cells, osteoclast-like cells • Location: end of bone, mostly epiphysis or metaphysis • Cells involved in bone remodeling:
      • Osteoprogenitor cells (MSC), osteoblast, lining cells, osteocytes, osteoclast • Osteoclast normal function: resorbs bone, pumps hydrogen into environment, acidic environment
    • Malignancy in giant cell tumor: • High-grade sarcoma arising in/next to giant cell tumor • Rare: resection and chemotherapy response • Primary osteosarcoma:
      • Rb and p53 mutations
      • High genetic instability, chromothripsis, and kataegis

    Hereditary Forms of Cancer

    • Germline genetics: hereditary disease and mendelian inheritance patterns
    • Somatic genetics: acquired DNA changes during tumor development
    • The multistep nature of cancer: time is an enemy, and cells are exposed to intrinsic mutation processes
    • Genetic instability: when a cell has a mutation in a gene important for DNA protection
    • Countermeasures: DNA damage repair mechanisms
    • Driver events: • Activated oncogenes • Defective tumor suppressor genes (Rb and p53) • Cancer usually develops during later decades of life
    • Inheritance patterns: • Autosomal dominant • Autosomal recessive • X-linked

    Paget's Disease of Bone

    • Increased bone resorption and formation
    • Primary abnormality resides in osteoclasts
    • Dense, inactive, and largely acellular bone
    • Increased risk of osteosarcoma (0.15-1%)

    Hereditary Colorectal Cancer

    • 10% of patients with melanoma have a positive family history
    • Familial clustering of melanoma is caused by pathogenic gene variants in CDKN2A, BAP1, POT1, TERT, TERF2IP, ACD, MITF, NEK11
    • Understanding the genetic basis of melanoma susceptibility gives insight into tumor suppressor mechanisms and provides opportunities for personalized surveillance, prevention, and treatment
    • Normal histology: • Layers: epithelial, lamina propria, muscularis mucosa, submucosa • Polyps: almost all colon carcinomas start with a polyp • Hyperplastic polyp: serrated lumina, no dysplasia • Tubulovillous adenoma: darker morphology, no dysplasia • Dysplasia: hyperchromasia, enlarged nuclei, disturbed growth patterns, mitosis • Adenocarcinoma colon: submucosal proliferation of glands
    • Development of colon carcinoma: • Stepwise process • Accumulation of mutations • Morphologic features increasing during progression
    • Hereditary colon cancer: • Familial Adenomatous Polyposis (FAP) • Lynch syndrome (non-polyposis syndrome) • MUTYH-associated polyposis (MAP)

    Microscopy and Pathology of Nephrosclerosis

    • Glomerulosclerosis: fibrotic scarring of glomeruli
    • Most common cause of end-stage renal disease is aging
    • Glomerulosclerosis: nomenclature • Focal: <50% of all glomeruli involved, majority showing sclerosis • Segmental: majority of involved glomeruli show sclerosis in <50% of cut surface
    • Incidence of focal global glomerulosclerosis with age
    • Causes: • Ischemia • Inflammation • Endocrine • Epithelial damage • Infection • Hyperperfusion • Unknown ('primary FSGS')

    Immune Complexes and Glomerulosclerosis

    • Relation between glomerular localization of immune complexes and clinical picture
    • Antibodies play a major role in inflammation
    • Anatomy of the kidney: • Glomerulus: a ball with one big/long capillary • Bowman capsule: capsel around the capillary
    • 4 localizations for deposits of immune complexes: • Under the sub-endothelium • Under the epithelium • In the mesangium • In the glomerular basement membrane### Nephritic Syndrome
    • Characteristics:
    • Hematuria
    • Renal dysfunction
    • Hypertension

    Immune Complex Deposits

    • Sub-endothelial deposits:
    • Antibodies bind to molecules in the glomerular basal membrane (auto- or allo-antigens)
    • Antibodies bind to the FC tail, attracting and activating complement precursors
    • Complement attracts granulocytes, leading to degranulation and protease production
    • Proliferation, blocking blood flow, and activating the renin-angiotensin system (RAS)
    • Leading to renal dysfunction and hypertension
    • Sub-epithelial deposits:
    • Antibodies bind to epitopes in the sub-epithelial space (auto- or allo-antigens)
    • Fc tail sticks out of the membrane, attracting complement precursors
    • Frustrated chemotaxis, leading to granulocyte accumulation and irritation
    • Eventual proteinuria, hypo-proteinemia, and edema

    Membranous Glomerulopathy

    • Stages:
      1. Sub-epithelial deposits
      2. Thickening of the basal membrane due to abnormal production
      3. Basal membrane encapsulation of complexes
      4. Scarred basal membrane with holes
    • Treatment:
      • Anti-inflammatory drugs
      • Protein-free diet

    Mesangial Deposits

    • Causes:
      • Abnormal antibodies (e.g. IgA nephropathy)
      • Auto-antibodies against molecules in the mesangium (e.g. laminin)
    • Characteristics:
      • Microscopic hematuria
      • Slow inflammation leading to scarring, accumulation of extracellular matrix, and decreased filtration area
      • Hypertension and renal dysfunction

    Diabetic Nephropathy

    • Characteristics:
      • High glucose levels and oxygen radicals harm endothelial cells and podocytes
      • Thickening of the basal membrane, increasing blood pressure, and albuminuria
      • Vascular alterations: loss of fenestrae, glycocalyx, and fenestrae, endothelial swelling, and arteriolar hyalinosis
    • Vascular Endothelial Growth Factor (VEGF) role:
      • Fundamental regulator of microvasculature
      • Produced by podocytes and diffuses to endothelium
      • Binding to VEGF receptor 2 on endothelial cells maintains endothelial cells and glycocalyx
      • Upregulation in diabetic mouse, but downregulation in human diabetic nephropathy

    Treatment of Diabetic Nephropathy

    • VEGF inhibition:
      • In diabetic mice, VEGF inhibition reduces proteinuria and improves renal function
      • In humans, sFlt-1 treatment reduces albuminuria, hypertrophy, and mesangial matrix expansion
      • sFlt-1 binds to M2 macrophages, reducing inflammation and endothelial activation

    Kidney Function and Failure

    • Kidney function:
      1. Production of urine
      2. Excretion of wastes
      3. Blood pressure regulation
      4. Production of erythropoietin
      5. Activation of vitamin D
      6. Acid/base regulation
    • Kidney failure:
      1. Volume overload
      2. Accumulation of toxic waste
      3. Hypertension
      4. Anemia
      5. Bone mineral disease
      6. Metabolic acidosis

    Acute Renal Insufficiency

    • Tubule-interstitial:
      • Allergic, autoimmune, hypoxic, or allograft rejection
    • Glomerular:
      • Nephritic (red blood cells in the urine)
      • IgAN, TBMN, Alport, vasculitis, and allograft glomerulitis
      • Nephrotic (no red blood cells in the urine)
      • DM-N, FSGS, minimal change, and allograft glomerulopathy

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    Description

    This quiz covers the basics of human growth and development, including measurements, genetic and environmental factors affecting height, and definitions of tall and short stature.

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