Shanklin 2

Shanklin 2
Subjects on schedule mean nothing.
Today we will overview/review general pathological concepts.
Injury- in pathology means something that happens to cells or tissues. Injury is disturbance from balanced, normal state (homeostasis). Balancing mechanisms are built in to overcome this problem up to a point. Homeostasis means various forces are in balance. Normality is a functional range. Homeostasis happens within and without that range. Body chemistry- talking about a mixture of forces that maintian a certain pH, concentration, rate of secretion. For example, Cl- content of human saliva-abundant. Hypersalivate and don’t swallow- lose a lot of Cl. Body is set up in balance.
Circadian rhythms make a difference in cetain injuries. Corticosteroids low in the morning and high in the afternoon. Say someone has 2nd degree burns over 50% of body. MRSA makes this a real and risky problem. Person burned- steroids released. ACTH from anterior pituitary stimulated by hypothalamus → neuroendocrine reaction to injury. Surge overrides circadian rhythm. Level of corticosteroids goes down in anterior pituitary- extremely depleted- takes 72 hours to restore. Debridement at 72 hours would result in further depletion. Burns can become lethal if treatment pattern augments pattern of injury.
What about myocardial infarction?
Sequence of pathogenesis:
Functional imbalance between cardiac muscle need and oxygen supply. Obstruction in artery, or narrowing of artery plus blood loss from trauma or stomach ulcer. Area undergoes necrosis. Area near outer part has extra blood flow. Organ continues to function. Keel over dead- not an infarction. How does body respond to infarction? There is collateral supply in heart- if artery is completely blocked- boundaries of infarct speak of competency of collateral supply. Even after infarct some of collateral supply comes in to help with restoration process. Cells begin exuding potassium and magnesium. Potassium loss is important. Serum potassium high enough- functional range is narrow. Heart stops at either end. Volume of heart knocked out and it still work= volume of functional reserve. 50% of lung is necessary. Kidney- about 70% is extra. Liver can remove 90% rat, 75% human. It regenerates to some degree. Half of spleen can be lost. Location of infarct in heart is critical. Infarct in superior part of interventricular septum interferes with function. In a zone of left ventricle can have up to 80% destroyed. PMNs move in. Endothelium stimulated. Boundary created. Macrophages gobble debris. Fibroblasts invade. Granulation tisue forms. Fibrous scar laid down. Collagen begins to contract and pulls in muscle. Problem is in PMN leukocytes. Proteolytic enzymes of PMNs can weaken the fibrous network enough for cardiac rupture. More PMNs present 7-8 days after attack- defense mechanism can become pathological.
Long term process of healing using the innate inflammation system is :
Injury, reaction, stabilization, restitution, healing. There may be restoration of effective function. Lenticulostriate artery of brain interferes with internal capsule of fibers that go from cortex to muscles in the event of a stroke. Brain-get polys and macrophages (microglia and outside ones). Loose fibrillar mass from astrocytes forms. Get space instead of collapse. If stroke hits voice center, functional problem results. Brain is plastic, though, and can be retrained.
Lung has built in collateral supply. Bronchial and pulmonary arteries. Bronchials bring in 10-15% of flow, consisting of oxygenated blood. Main stream of pulmonary artery is curve to right, right angle to left. Embolus causes infarct of lung. Get PMNs, macrophages, restorative process.
Adaptive side works differently. If did not have scar production through innate system, could not have surgery. More damage from retractors than scalpel.
Body will heal any injury if you give it time and do not disturb it farther. Reinjury is not good. Reinjury sets into motion everything we have talked about. If organism is immune challenged, adaptive system comes into play. Reason no immune reaction to simple cut, is that you prevent sensitization from bacteria or viruses. How long to develop lymphocyte ability to respond to bacteria or virus? 5 to 6 Days. Lymph nodes there- get response. Th, B, plasma cells. Secondary reaction is humoral through antibodies. Plasma cell life in tissue is a few days. Plasma cell infiltration is a sign of active chronic inflammation. When you stop seing them- inactive chronic inflammatory reaction. T cells are stimulated by IL-2. If stimulate lymphocyte clone with IL-2, get expansion. Add more- they die. Receptor density and receptor affinity are involved. Fill low affinity ones- get secondary decline. In vivo- not that simple. Lots of secondary feeds.
How does bone marrow “know” that you have a thorn in your thumb? Signal not through brain. Leukotaxin means “to move white” . Cells release peptides to lymphatics to marrow cells. Cells sense concentration gradient. Deep inside tissue- lymphatic has epithelial tissue. Tissue altered to HEV, with selectins on surface. Adult marrow cannot be weighed- roughly 1500g scattered all over. We do not know if nearest marrow responds or not. Dilution of message occurs, but it is sufficient. Couple of molecules leucotaxic peptide- get a bit of pus formation in wound. If immune injury occurs at same time, move into adaptive response. Sutures stimulate dense scar around them to preclude secondary response.
Tomorrow- genetic pathology.
Start with a cell called a leukoblast in marrow. Goes through steps and wind up with PMN, or called neutrophil. Appearance varies by preparation. Different in smear or in tissue. PMN has lobation of nuclear material in cell. Hypersegmented in pernicious anemia occurs in B-12 or folate deficiency. Normal life span 10 days -2 weeks. Activated- 1-2 days. Pelger-Huet anomaly- does not segment at all. Myelocyte band form (nucleoplasm is band across center of cell) is immature. Bad bacterial infection- band form released. P-H anomaly stops at band form. It is a genetically dominant trait. Sufficiently uncommon that it is unk whether it is one allele or 2. P-H relationship with TB is contributory to establishment of chronic infection. Hard to kill mycobacteria. Acquired P-H anomaly how to account for it? There could be cellular factors promoting hyposegmentation.