Clinical Correlations Flashcards
What are 2 dysfunctions that can happen with occluding junctions?
Increased permeability of occluding junctions results in decreased barrier selectivity
Pathogens target occluding junctions - if they make them dysfunctional, they remove physical barrier to invasion
Claudin 14 mutation
Mutation in protein in occluding junctions that makes those junctions more permeable in organ of corti (affects sound receptor cells)
Can’t generate action potentials
Hereditary form of deafness
H. pylori
Disrupts occludin function or recruits it to the apical domain (from lateral)
Bacteria removes occludin junction barrier and can travel between cells lining the stomach to invade tissue below
What can happen if anchoring junctions are dysfunctional?
Cells can dissociate from each other because of the lack of lateral anchoring
Cells can delaminate from basement membrane without basal anchoring
Pemphigus Vulgaris
Blistering condition
Autoantibodies against cadherins in desmosomes which causes loss of desmosome function (link adjacent cells - lateral domain).
Cells come apart but basal cells remain linked to basement membrane
Bullous Pemphigoid
Blistering Condition
Autoantibodies against type XVII collagen, one of hemidesmosomes TMPS. Loss of hemidesmosomes function that links cells to basement membrane.
Entire epithelium detaches from basement membrane but cells stay linked to adjacent cells
What are carcinomas? How are they classified
Malignant cancers that originate in/from epithelial tissue.
Classified by how far they have spread and based on type of epithelium involved
Why does stress age you?
Cortisol inhibits fibroblast growth and division as well as collagen and elastin deposition
When can inactive fibroblasts reactivate?
Wound healing
White cells usually do not divide. When is the exception?
Morbid Obesity.
When can white fat cells redifferentiate?
Beiging of white fat - become brown fat cells
Results from caloric restriction (gastric bypass, intermediate fasting), or repeated cold exposure
What are Type I hypersensitivity reactions?
Antigens (allergens) cause plasma cells to make IgE antibodies. IgE antibodies bind receptors in cell membrane of mast cells and basophils -> Mast cells now sensitized
Subsequent exposure to allergen binds to IgE antibodies in mast cells and triggers degranulation.
Release of histamine initiates inflammatory response and is also responsible for symptoms associate with allergic reaction
What are the effects of histamine?
Increases blood flow to area - vasodilator
Increases blood vessel permeability - swelling
Increase mucus production
Causes contraction of smooth muscle of bronchi
What is heparin?
Anticoagulant
Binds and inactivates histamine
Modulates intensity of allergic response
Why are mast cells not in CNS?
Inflammation during allergic reactions would cause potentially disruptive edema in CNS - no room for tissue expansion because of skull
Increased permeability of brain capillaries
Benign tumors derived from white fat tissue
Lipomas
What happens when body fat composition is changed?
Affects hormones that regulate metabolism, fat storage, insulin resistance, and inflammation. And thus, one’s ability to gain/lose fat easily
What occurs with hyaline cartilage with age?
Hyaline cartilage in costal cartilage and large airways tend to calcify with age and replaced with bone in geriatric patients.
Perichondritis
Perichondrium infection - pathogens usually enter the area during or after injury. Easier to travel through perichondrium ECM than cartilage matrix.
Common location is perichondrium surrounding elastic cartilage in the pinna of the ear due to ear piercing, sports injury, and ear surgery
What occurs if fibrocartilage is the annulus fibrosis is thinned or damaged?
The nucleus pulposus starts to bulge outward and compress spinal nerve roots.
What does osteoarthritis stem from?
Lesions stem from degeneration of articular cartilages and disordered cartilage repair.
Articular cartilage is lost, exposing subchondral bone. Subchondral cysts form loss of subsurface spongy bone and synovial fluid leaks into bone.
What is cauliflower ear?
Shearing or impact forces can cause a hematoma to form in pinna of ear.
Vessles of perichondrium are damaged, disrupting circulation.
Blood accumulates between perichondrium and underlying cartilage, physically blocking nutrient and oxygen diffusion to avascular cartilage - ishcemia
Hematoma is replaced by disorganized scar tissue and fibrocartilage - fibrosis and contracture causes tissue to sag and kink and forms lumpy cauliflower appearance
What reshapes bony tooth sockets during orthodontic treatments to align and straighten teeth?
Combination of pressure and tension applied to bone
What are bone morphogenic proteins used in?
Used after bone surgeries involving large bone defects, bone grafts, and spinal fusions
Stimulate bone formation and promote bone healing
What occurs if there are insufficient minerals in bone matrix?
Bone is too soft
Rickets in children and Osteomalacia in adults.
Osteoid does not mineralize sufficiently so you have softer and weaker bone tissue. Common cause is vitamin D deficiency
What occurs when collagen I is malformed or insufficient in bone tissue?
Bone is brittle
Osteogenesis Imperfecta - “brittle bone disease”
What are the clinical markers of osteoblast activity?
Serum levels of ALP and osteocalcin - elevated with increased osteoblast activity
Also higher during childhood and puberty because of bone growth and development
Also elevated in metabolic diseases associated with increased bone or osteoid formation
What are bone lining cells and where are they?
Inactive osteoblasts in endosteum
Cover internal bone surface and protects bone surfaces from osteoclasts
What needs to occur following periodontal surgery where periosteum and overlying gum tissue are reflected?
Periosteum must be carefully re-applied to any exposed bone to prevent osteoclastic bone resorption
What does fibrin have to do with clotting?
Clotting is the conversion of fibrinogen to fibrin (by thrombin)
Fibrin fibers form a branching 3D net that traps RBCs and platelets.
What does too much clotting lead to?
Thrombosis - clots that block blood flow
What does too much fibrinolysis lead to?
Excessive bleeding
What occurs if there are large numbers of immature blood cells in circulating blood?
Body is running out of the mature form of that blood.
Immature cells are not released into the bloodstream unless there are not enough mature blood cells available to deal with an urgent situation
What occurs if there are defect in the spectrin-actin grid or in the intracellular attachment proteins connecting the grid to the cell membrane of RBCs?
Malformed RBCs which causes reduced surface area and flexibility
What is the mean corpuscular volume (MCV) in a CBC?
A measure of how much hemoglobin each RBC can hold
What is polycytemia?
Erythrocytosis
Increased RBC mass in circulating blood and blood is too viscous so there is a risk of thrombosis
What are anemias?
Hemoglobin in circulating blood insufficient to meet oxygen needs - symptoms result from low oxygen
Anemia is a syndrome and many thing cause low hemoglbin
CBC values vary depending on cause of anemia
How does cell shape relate to anemia?
Conditions that affect RBC size, color, or shape cause anemia
Abnormal shape = reduced MCV = less hemoglobin
An altered shape means RBCs are less flexible and can damage capillaries
What can high numbers of abnormally shaped RBCs result from?
Problems during RBC development
Problems with Hb molecules or its synthesis
Problems with splenic macrophages - can’t remove abnormal RBCs from circulation
What is the relevance of immature RBCs on a CBC?
Elevated number of immature RBCs indicated increased or severe damage for new RBCs
Available supply of mature RBCs can’t meet oxygen demands so immature RBCs are sent to help but they are less efficient at gas transfer vs mature RBCs.
When are band cells released from bone marrow?
When there is a dire need for neutrophils such as in severe and acute infections
Acute Intermittent Porphyria
Enzyme deficiency in porphobilinogen deaminase (step 3)
Accumulation of ALA and porphobilinogen in serum and urine
Clinical features: Acute episodes of abdominal pain, urine dark red-colored, and alcohol can exacerbate this disease.
Porphyria Cutanea Tarda
Enzyme deficiency in uroporphyrinogen decarboxylase (step 4)
Accumulation of uroporphyrin in urine (emits pink fluorescence under UV light)
Generation of reactive oxygen species (ROS)
Clinical features: skin lesions caused by uroporphyrin-triggered ROS release. Alcohol and iron overload can exacerbate the disease
What are disease conditions that may cause jaundice?
Hemolytic crisis - prehepatic jaundice
Hepatic damage - hepatocellular jaundice
Bile duct occlusion - posthepatic or cholestatic jaundice
What is the jaundice when albumin cannot bind excess bilirubin, liver cannot conjugate excess bilirubin, and elevated unconjugated (indirect) serum bilirubin moves to brain (kernicterus) and skin, eyes (jaundice), but the feces and urine are normal in color?
Preheaptic Jaundice - Hemolytic Crisis
Conditions predisposing - G6PDH deficiency and Sickle cell crisis, and Rh disease in newborn (newborn jaundice)
What is hepatic jaundice? What conditions cause it?
Liver damage.
Condition that can cause are infections, liver cirrhosis, liver cancer, and alcohol and drugs.
Occurs when unconjugated (indirect) bilirubin increases in plasma and tissues. High serum ALT and AST. Pale color of urine and feces
What are genetic causes of hepatic jaundice?
Liver is normal
Crigler Najjar and Gilbert syndrome - deficiency UGT enzyme
Temporary newborn jaundice - UGT enzyme immaturity
What is posthepatic jaundice?
Bile duct occlusion
Conjugated bilirubin is excreted by the kidney
Urine is dark orange
Pale feces - little to no fecal bilirubin or urobilin
Presence of alkaline phosphatase in the serum
What are the clinical lab findings of post-hepatic jaundice?
Serum - highly elevated conjugated bilirubin in the blood
Urine - Bilirubin present
Other - High serums alkaline phosphatase
Pale feces, orange urine
What are the clinical findings of hepatic jaundice?
Serum - Total and unconjugated bilirubin elevated in the blood
Other - High serum ALT and AST
Urine and feces are pale, may cause kernicterus
What are clinical lab findings of prehepatic jaundice?
Serum - total and/or unconjugated bilirubin slightly elevated in the blood
Urine - No bilirubin
Other - Low hemoglobin, higher reticuloyte count
May cause kernicterus. urine and feces are normal in color
