McNeil's notes - Wound healing, fluids, heme (-coag), endo Flashcards
Arrange the listed phases of wound healing in the appropriate order.
- Vasoconstriction
- Collagen synthesis
- Epithelialization
- Contraction
- Vasodilation
- PMN infiltration
1 5 6 3 2 4
vasoconstriction, vasodilation, PMN, epitheliazation, collagen synthesis, collagen maturation
I. Inflammatory Phase A) Immediate to 2-5 days B) Homeostasis Vasoconstriction Platelet aggregation Thromboplastin makes clot C) Inflammation Vasodilation Phagocytosis
II. Proliferative Phase
A) 2 days to 3 weeks
B) Granulation
Fibroblasts lay bed of collagen
Fills defect and produces new capillaries
C) Contraction
Wound edges pull together to reduce defect
D) Epithelialization
Crosses moist surface
Cell travel about 3 cm from point of origin in all directions
III. Remodeling Phase
A) 3 weeks to 2 years
B) New collagen forms which increases tensile strength to wounds
C) Scar tissue is only 80 percent as strong as original tissue
Which of the following is the first cell type to appear in a wound?
a) neutrophils
b) lymphocytes
c) macrophages
1) neutrophils
Within first 24 hours
a. Neutrophils are the predominant cell type
b. This is the phase of acute inflammation
c. Epithelial cells start proliferating and migrating into the wound cavity
2) At 72 hours, what is the predominant cell type in a clean cut wound?
a) fibroblasts
b) macrophages
c) PMNs
d) monocytes
b) macrophages
By the 2nd and 3rd day
a. Macrophage and fibroblasts are the dominant cell types
b. Epithelial cell proliferation and migration continues
c. Angiogenesis begins
d. Granulation tissue appears
e. Collagen fibres are present but these are vertical
f. They do not bridge the wound gap
g. Granulation tissue comprises newly formed new capillary loops
3) Which cell is predominant in the 5th day in wound healing :
a. Neutrophils
b. Macrophages
c. Fibroblast
d. Myofibroplast
e. None of the above
3) Fibroblast
By the end of 5th day
a. Fibroblasts are the predominant cell type
b. They synthesize collagen
c. Collagen now bridges the wound edges - bridging collagen
d. Epidermal cells continue division and epidermis is now multi-layered
e. Abundant granulation tissue is present
4) Which cell is highest in number in a healing wound after 5 days?
a) Neutrophils
b) Macrophages
c) Keratinocytes
d) Fibroblasts
e) Myofibroblasts
d) Fibroblasts
During 2nd week
a. Acute inflammation begins to reduce
b. Collagen continues to accumulate
The inflammatory stage of healing :
a) Decreased by early epithelialization.
b) Increased by split thickness skin graft.
c) Not present in healing by primary intention.
d) Precedes proliferative stage.
d) Precedes proliferative stage.
Macrophages are the most predominant cell type in which phase of wound healing? A. Lag phase B. Proliferative phase C. Maturational phase D. Remodelling phase
Answer: Lag phase
Macrophages and neutrophils are predominant during the inflammatory phase [AKA lag phase] (peak at days 3 and 2, respectively)
- Townsend: Sabiston Textbook of Surgery, 18th ed.
The proliferative phase of wound healing is characterized by which cell type:
a) mast cells
b) neutrophisl
c) lymphocytes
d) macrophages
e) fibroblasts
e) fibroblasts
What cell type is responsible for the remodeling phase?
a. fibrils
b. myofibroblasts
c. PMNs
d. Macrophages
Answer: myofibroblast = fibroblast that has gained actin/myosin
When does granulation tissue formation stop:
a. When collagen break down is more than synthesis.
b. When re-epithelialization is complete.
c. When hypoxia exists in the tissues.
d. After 6 months
Answer: When re-epithelialization is complete
The proliferative phase involves the formation of a collagen matrix and granulation tissue and then epidermal cell migration over the matrix.
- Habif: Clinical Dermatology, 5th ed.
Fetal wound healing. All are true except
- No scar
- minimal tgf Beta
- dec hyaluronic acid
b) No scarring
Fetal skin wounds heal rapidly and without the scarring and inflammation that are characteristic of adult skin wounds.
Fetal wounds have been demonstrated to have minimal levels of TGF-β and FGF-2 by immunohistochemistry.
Levels of hyaluronic acid are persistently elevated in fetal wounds
- Sabiston
The fetal environment, an extrinsic difference between fetal and adult wounds, is characterized by a hyaluronic acid–rich amniotic fluid. Studies suggest that the increased number of hyaluronic acid receptors and increased amount of hyaluronic acid may create a permissive environment in which fibroblast movement is facilitated and thereby results in the increased rate and efficiency of fetal healing.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
Collagens I, III, V, and VI appear earlier and the ratio of type III to type I is greater in fetal wounds, which is consistent with the higher prevalence of type III collagen in normal fetal tissue. Fetal fibroblasts in vitro have higher collagen production than their adult counterparts do. This may be secondary to the unique regulatory mechanism for prolyl hydroxylase and may explain why there is higher fibroblast activity in fetuses younger than 20 weeks’ gestation. Collagen synthesis falls to adult levels after 20 weeks’ gestation.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
What is the cytokine responsible for the proliferation of fibroblasts:
a) TGF
b) TNF alpha
c) TGF beta
d) IL-8
As the concentration of TGF-β rises in the inflammatory site, fibroblasts are directly stimulated to produce collagen and fibronectin, thus leading to the proliferative phase.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
TGF-b for fiBroBlasts
Which factor stimulates angiogenesis? A. Basic fibroblast growth factor B. C5a/C3a C. Decreased wound O2 tension D. IL1
Angiogenesis appears to be stimulated and manipulated by a variety of cytokines predominantly produced by macrophages and platelets. As the macrophage produces TNF-α, it orchestrates angiogenesis during the inflammatory phase. Heparin, which can stimulate the migration of capillary endothelial cells, binds with high affinity to a group of angiogenic factors. VEGF, a member of the PDGF family of growth factors, has potent angiogenic activity. It is produced in large amounts by keratinocytes, macrophages, and fibroblasts during wound healing. Cell disruption and hypoxia, hallmarks of tissue injury, appear to be strong initial inducers of potent angiogenic factors at the wound site, such as VEGF and its receptor. Both acidic and basic FGFs, or FGF-1 and FGF-2, are released from disrupted parenchymal cells and are early stimulants of angiogenesis. FGF-2 provides the initial angiogenic stimulus within the first 3 days of wound repair, followed by a subsequent prolonged stimulus mediated by VEGF from days 4
through 7.
- Townsend: Sabiston Textbook of Surgery, 18th ed
Stimulants of angiogenesis: FGFs TNF-α TGF-α VEGF
α = αngiogenesis
Normal healing is accelerated by which of the following?
a. Ascorbic acid.
b. Vitamin A.
c. Zinc.
d. Increased local oxygen tension.
e. Scarlet red.
Vitamin A can help, but only to prevent steroid effect.. I don’t know what the answer is here - probably mis-remembered stem
Zinc and Vit C can help if you are deficient
Occlusion of wounds leads to faster healing. The process of neovascularization within granulation tissue is stimulated by hypoxic conditions such as those that occur beneath occlusive, oxygen-impermeable dressings. Occlusive dressings prevent crust formation and drying of the wound bed. The rate of epithelialization is faster under occlusive dressings. Wound fluid under occlusive dressings is favorable to fibroblast proliferation. Adhesive occlusive dressings may remove newly formed epithelium.
Malnutrition interferes with healing. Vitamin C and zinc deficiencies lead to poor healing. Systemic steroids in a dosage greater than 10 mg a day interfere with healing.
- Habif: Clinical Dermatology, 5th ed.
What is true about epithelialization:
a. Can be inhibited by infection
b. Begins only from the edges
c. ??????
d. ????
Answer: Can be inhibited by infection
Dermal appendages make epithelialization
Epithelialization:
Restore the normal external barrier. Proliferation and migration of epithelial cells adjacent to wound. Occurs within one day and is seen as thickening of epidermis at wound. The marginal basal cells at the wound edge lose their attachment to underlying dermis, enlarge and migrate across the surface of the provisional matrix. Fixed basal cells rapidly divide and migrate via a ‘leap-frogging’ action (one over the other). Once the deficit is covered with epithelial cells it will flatten out and become more columnar in shape and cells will increase their mitiotic activity. Will eventually keratinize. For approximated wound edges will get re-epithelization within 48hrs. If defect is larger the process will take longer. Stimulus is felt to be due to loss of contact inhibition, exposure of extracellular matrix (esp fibronection) and cytokines (TGF-beta and EGF, PDGF etc….)
- Schwartz 2005
Keratinocytes located at the basal layer of the residual epidermis or in the depths of epithelium-lined dermal appendages migrate to resurface the wound.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
Bone inflammation healing question. What type of cell appears?
In the inflammatory phase of fracture healing, a hematoma is formed from the blood vessels ruptured by the injury. Inflammatory cells invade the hematoma and initiate the lysosomal degradation of necrotic tissue. Bolander suggested that the hematoma is a source of signaling molecules, such as transforming growth factor (TGF)-b and platelet-derived growth factor (PDGF), which initiate and regulate the cascades of cellular events that result in fracture healing.
- Canale & Beaty: Campbell’s Operative Orthopaedics, 11th ed.
Reperfusion limb injury. Include all of the following except:
a. compartment syndrome
b. hypercalcemia
c. hyperkalemia
d. lactic acid increases
e. myoglobin increases
b. hypercalcemia
Reperfusion Syndrome
The resulting myonephropathic syndrome, with its associated hemodynamic instability, lactic acidosis, and hyperkalemia, is well recognized by surgeons. Myoglobinuria may persist for 2 to 4 days after reperfusion.
Acute compartment syndrome results as pressure increases beyond capillary perfusion pressure (30 mm Hg) and tissue perfusion is impaired.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
Other mediators of cell injury, such as calcium, may also enter reperfused cells, damaging various organelles, including mitochondria, and increasing the production of free radicals.
- Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed.
A patient post op day seven now requires another operation through the same incision. The incision will then:
a. heal more slowly
b. heal faster
c. heal depending on nutritional status
d. heal exactly the same rate
Answer: heal faster
- Secondary healing effect: when a normal healing wound if disrupted after the 5th day and then reclosed, the return of wound strength is more rapid than with primary healing
- Due to elimination of lag phase present in normal primary healing
- Monocytes must be present for wound to heal
- Neutrophils are not necessary in wound and healing can proceed without them
Which is most responsible for minimizing wound contraction?
a) FTSG
b) STSG
c) Normal skin tension
d) Collagen
e) Procollagen
??
Why is scar tissue not as strong as normal skin?
Answer: rete pegs
Remodeling
The fibroblast population decreases and the dense capillary network regresses. Wound strength increases rapidly within 1 to 6 weeks and then appears to plateau up to 1 year after the injury (see Fig. 8-8 ). When compared with unwounded skin, tensile strength is only 30% in the scar. An increase in breaking strength occurs after approximately 21 days, mostly as a result of cross-linking. Although collagen cross-linking causes further wound contraction and an increase in strength, it also results in a scar that is more brittle and less elastic than normal skin. Unlike normal skin, the epidermodermal interface in a healed wound is devoid of rete pegs, the undulating projections of epidermis that penetrate into the papillary dermis. Loss of this anchorage results in increased fragility and predisposes the neoepidermis to avulsion after minor trauma.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
Keloid scar: all except
a. familial
b. Respond specifically to intralesion injection of triamcinolone
c. Commonly in the back
d. Common in white people
Answer: Commonly in white people
Also not that common in the back. This question was probably remembered wrong
- AD genetic transmission in mostly dark skinned people
- Typically develops several months after injury and rarely subside
- On trunk above clavicles, upper extremities, and face
- Extends beyond the margin of the original tissue injury, behaving like a benign tumour
- Contain an over abundance of collagen without increased numbers of fibroblasts
- Cause unknown
- Some improvement is usually seen with excision and one of: 1) intralesional steroid injection (triamcinilone); 2) short course radiotherapy but the resulting scar post radiation is unpredictable and can be worse.
- Radiation should be avoided (Schwartz p. 283)
- Other possible treatments:
- Pressure dressing
- Steroid-impregnated tape
- Silicone sheets
- Interferon- alpha has some reported
Keloids and hypertrophic scars are associated genetically with HLA-B14, HLA-B21, HLA-Bw16, HLA-Bw35, HLA-DR5, HLA-DQw3, and blood group A.
Corticosteroids, specifically intralesional corticosteroid injections, have been the mainstay of treatment. Corticosteroids reduce excessive scarring by reducing collagen synthesis, altering glucosaminoglycan synthesis, and reducing production of inflammatory mediators and fibroblast proliferation during wound healing. The most commonly used corticosteroid is triamcinolone acetonide (TAC) in concentrations of 10-40 mg/mL administered intralesionally with a 25- to 27-gauge needle at 4- to 6-week intervals.
Keloids form more frequently in Polynesian and Chinese persons than in Indian and Malaysian persons. As many as 16% of people in a random sampling of black Africans reported having keloids. White persons are least commonly affected.
Frequency of lesion sites
* In white persons, keloids tend to be present, in decreasing order of frequency, on the face (with cheek and earlobes predominating), upper extremities, chest, presternal area, neck, back, lower extremities, breasts, and abdomen.
* In black persons, the descending order of frequency tends to be earlobes, face, neck, lower extremities, breasts, chest, back, and abdomen.
* In Asian persons, the descending order of frequency is earlobes, upper extremities, neck, breasts, and chest.
- http://emedicine.medscape.com/article/1057599-overview
Treatment of Keloid includes all except:
a. Vit E
b. Intralesion steroid
c. Pressure
d. Interferon
e. silicon
a. Vit E
The effect of pressure therapy is cause by all except:
a. Reduce collagen fibers
b. Reduce the number of fibroblast
c. Cell death
d. ????
Prevention is key, but therapeutic treatment of hypertrophic scars and keloids includes occlusive dressings, compression therapy, intralesional corticosteroid injections, cryosurgery, excision, radiation therapy, laser therapy, interferon (IFN) therapy, 5-fluorouracil (5-FU), doxorubicin, bleomycin, verapamil, retinoic acid, imiquimod 5% cream, tamoxifen, tacrolimus, botulinum toxin, and over-the-counter treatments (eg, onion extract; combination of hydrocortisone, silicon, and vitamin E).
D’Andrea et al, from a case-control comparative study, reported resolution in 54% of the patients who had their keloids treated by a combination of surgical excision, silicon sheeting, and intralesional verapamil versus 18% in the control group without intralesional verapamil. The recurrence rate was 36% in the active group after 18 months of follow-up.
In a prospective, double-blinded, randomized clinical trial Jenkins et al reported no beneficial effect of either vitamin E or topical steroids when both treatments were applied post grafting procedures for reconstruction for postburn contractures
- http://emedicine.medscape.com/article/1057599-treatment
The effect of pressure therapy is cause by all except:
a. Reduce collagen fibers
b. Reduce the number of fibroblast
c. Cell death
d. ????
c. Cell death
In addition to silicone gel, pressure therapy following excision is effective and causes minimal adverse effects. The mechanism of pressure therapy has yet to be determined but may be through pressure-induced ischemia that promotes collagen degradation and modulates fibroblast activity.
- Davidson et al. A Primary Care Perspective on Keloids. Medscape J Med. 2009; 11(1): 18.
Which of the following is CORRECT regarding keloids?
a) They are best treated with radiation
b) They are best treated with steroids
c) They are more common in Caucasians
d) They are hisotlogically distinct from hypertrophic scars
e) They exceed the margins of the original wound
e) They exceed the margins of the original wound
Which factor is true regarding hypertropic scars?
a. Decreased total collagenase
b. Extension beyond boundary
c. Variable response to therapy
d. Increased type 3 collagen
a. Decreased total collagenase
- Histologically similar to keloid except they respect the boundaries of the original injury
- More frequent in Asians and Blacks
- Upper torso and flexor surfaces
- Develop within the first month then subside gradually
- Improvement: pressure garments, topical silicone sheeting applications, or excision and reclosure (only useful if the wound was not closed primarily or was complicated by infection.
Both MMP-1 (collagenase) and MMP-9 (gelatinase involved in early tissue repair) are decreased in hypertrophic scars and keloids.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
There are histologic differences between hypertrophic scars and keloids. Large collagen bundles occur in keloidal scars but not in hypertrophic scars.
- Habif: Clinical Dermatology, 5th ed.
During the formation of HS (hypertrophic scar), the increase of type I and decrease of type III are important, and the thick type I collagen is the fibrosis pathology background of scar tissue. The results of the experiment show that type I increased and type III decreased more obviously in the HS group than in the NS (normal scar) group.
- Qiu et al. A STUDY ON COLLAGEN CONSTITUTE AND AFFECTED FACTORS IN HYPERTROPHIC SCAR AT DIFFERENT AGE PERIODS. Annals of Burns and Fire Disasters - vol. XVI - n. 2 - June 2003
Which cytokine may reduce scar hypertrophy? A. EGF B. FGF C. IFN-gamma D. IL-2
Interferon-γ (IFN-γ), another proinflammatory cytokine, is secreted by T lymphocytes and macrophages. Its major effects are macrophage and PMN activation and increased cytotoxicity. It has also been shown to reduce local wound contraction and aid in tissue remodeling. IFN-γ has been used in the treatment of hypertrophic and keloid scars, possibly by its effect in slowing collagen production and cross-linking while collagenase (MMP-1) production increases.[7] Experimentally, however, it has been shown to impair re-epithelialization and wound strength in a dose-dependent manner when applied either locally or systemically. These findings suggest that administration of IFN-γ may improve scar hypertrophy by decreasing the strength of the wound.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
What contributes most to the strength of a two day old clean cut wound?
a. epithelialization
b. collagen cross linking
c. fibrin clot
d. amount of collagen
e. neovascularization
Answer: epithelialization
Within 24 hours, neutrophils appear at the margins of the incision, moving toward the fibrin clot. The epidermis at its cut edges thickens as a result of mitotic activity of basal cells, and within 24 to 48 hours, spurs of epithelial cells from the edges both migrate and grow along the cut margins of the dermis, depositing BM components as they move. They fuse in the midline beneath the surface scab, thus producing a continuous but thin epithelial layer.
- Coltran: Robbins Pathologic Basis of Disease, 6th ed
Wound strength at 3 days depends on: A. Fibroblast proliferation B. Epithelialization C. Sutures D. Collagen
Answer: sutures
Wound tensile strength at 7 days is most dependent on:
a) epithelialization
b) fibrin
c) collagen
d) ground substance
e) none of the above
Answer: collagen
Which tissue has the highest tensile strength three weeks after initial cut and surgical repair?
a. Facial skin
b. Small intestine
c. Tendon
d. Fascia
e. Cardiac muscle
Answer: Facial skin vs. Intestine
Remodelling phase of wound healing; all except?
a. Tensile strength increases due to collagen synthesis
b. Tensile strength increases due to cross-linking of collagen
c. Tensile strength plateaus at 3 months
d. Tensile strength achieves 80% of normal
e. Tensile strength declines during time
Answer: Tensile strength increases due to collagen synthesis
a. Tensile strength increases due to collagen synthesis (yes change from Type III to Type I; net result is less collagen but better collagen)
b. Tensile strength increases due to cross-linking of collagen (yes)
c. Tensile strength plateaus at 3 months (does plateau at 6 weeks but then continues to remodel upto years)
d. Tensile strength achieves 80% of normal
e. Tensile strength declines during time (increases)
Tensile strength correlates with total collagen content for approximately the first 3 weeks of wound healing. At 3 weeks the tensile strength of skin is 30% of normal. After this time, there is a much slower increase in the content of collagen until it plateaus at about 6 weeks. Nevertheless, tensile strength continues to increase as a result of intermolecular bonding of collagen and changes in the physical arrangement of collagen fibers. Although the most rapid increase in tensile strength is early during the first 6 weeks of healing, there is a slow gain for at least 2 years. The ultimate strength, however, never equals that of unwounded tissue, reaching a level only 80% of original skin strength.
- Rush Review of Surgery 3rd edition
When sutures are removed from an incisional surgical wound, usually at the end of the first week, wound strength is approximately 10% that of unwounded skin. Wound strength increases rapidly over the next 4 weeks, slows down at approximately the third month after the original incision, and reaches a plateau at about 70% to 80% of the tensile strength of unwounded skin. Lower tensile strength in the healed wound area may persist for life. The recovery of tensile strength results from the excess of collagen synthesis over collagen degradation during the first 2 months of healing, and, at later times, from structural modifications of collagen fibers (cross-linking, increased fiber size) after collagen synthesis ceases.
- Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed.
When does the tensile strength of a wound reach 80%:
a. In 4 weeks.
b. In 8 weeks.
c. In 12 weeks.
d. In 16 weeks
Answer: 8 vs 12 weeks
Wound strength gradually increases during the healing process. After 2 weeks, a wound has less than 10% of its final healed strength. By this time, most superficial or percutaneous closure materials are removed, and the resulting wound has little to rely on for strength unless additional support is available. Wound strength increases to 20% by 3 weeks and to 50% by 4 weeks. At 3-6 months, a wound achieves its maximum strength, which is 70-80% that of normal skin.
- http://emedicine.medscape.com/article/1127693-overview
As we all know, collagen once healed will never be as strong as it was originally (about 80%).
Dermis, intestinal submucosa, muscular fascia, tendon, ligament, Scarpa fascia and blood vessel wall represent a partial list of tissues with high collagen content. After 6 weeks, wounded tissue has gained about 50% of its eventual strength. To prevent hernia formation, heavy lifting is avoided after major abdominal surgery for six weeks. Tendon repairs are splinted and activity restricted to avoid full tension for a similar period of time.
- Greenfield CD, Ch. 3.
Which of the following does steroid therapy not do?
a) upregulate MHC I
b) downregulate TNF
c) downregulate IL-1
Answer: ? upregulate MHC I
Steroids downregulates MHC II … likely the right answer
GLUCOCORTICOIDS EFFECTS (14)
1. Suppress IL-2 production
2. Inhibit lymphocyte activation
3. Inhibit neutrophil migration to areas of inflammation
4. Inhibit monocyte migration to areas of inflammation
5. Inhibit histamine release and histamine-induced lysosomal degranulation by mast cells
6. Inhibit B cell activation and proliferation at high doses
7. Retards entry of free water into cells
8. Decreases capillary permeability to water
9. Weak mineralocorticoid effect
10. Stimulation of angiotensin release (maintains BP)
11. Inhibits PGI2 (potent vasodilator) → maintenance of BP
12. Impaired collagen mRNA transcription and fibroblast activity
13. Inhibit osteoblast activity
14. Promotes early closure of epiphyseal plates in kids
Long term effects (5):
1. Catabolic state with negative N balance
2. Redistribution of body fat → truncal obesity
3. Emotional and psychological disturbances
4. Cataracts
5. Corneal ulcers
- Morell Notes
Prednisone affects wound healing by each of the following EXCEPT:
a) inhibition of neovascularization
b) inhibition of transcription of mRNA for type I collagen
c) inhibition of transcription of mRNA for type III collagen
d) inhibition of collagenase
e) stabilizing lysosomes
f) increasing alpha2 macroglobulin
Answers provided:
1) increase alpha 2 macroglobulin
2) inhibition of collagenase
GCSs down-regulate type I collagen gene expression by transcriptional and posttranscriptional mechanisms and up-regulate collagenase 3 expression by posttranscriptional mechanisms. Collagenase 3 from osteoclasts and chondrocytes breaks down type I and II collagen, the major components of bone and cartilage matrix. Matrix proteins are decreased, and proteases for matrix destruction are increased. These effects on bone and cartilage may be mediated partially by GCS inhibition of insulin-like growth factor I.[19]
- Update on systemic glucocorticosteroids in dermatology. Dermatologic Clinics. Volume 19 • Number 1 • January 2001
Glucocorticosteroid impairs fibroblast proliferation and collagen synthesis. The amount of granulation tissue formed is also decreased. Steroids stabilize the lysosomal membranes. This particular effect can be reversed by the administration of vitamin A. The decrease in breaking strength caused by the administration of exogenous steroids appears to be both time and dose related.
- Townsend: Sabiston Textbook of Surgery, 16th ed., Copyright © 2001 W. B. Saunders Company
[B]lunting of angiogenesis by steroids may be related to the inhibition of growth factor production.
- Middleton: Allergy: Principles and Practice, 5th ed.,
Glococorticoid effects:
- Suppress IL-2 production
- Inhibit lymphocyte activation
- Inhibit neutrophil migration to areas of inflammation
- Inhibit monocyte migration to areas of inflammation
- Inhibit histamine release and histamine-induced lysosomal degranulation by mast cells
- Inhibit B cell activation and proliferation at high doses
- Retards entry of free water into cells
- Decreases capillary permeability to water
- Weak mineralocorticoid effect
- Stimulation of angiotensin release (maintains BP)
- Inhibits PGI2 (potent vasodilator) → maintenance of BP
- Impaired collagen mRNA transcription and fibroblast activity
- Inhibit osteoblast activity
- Promotes early closure of epiphyseal plates in kids
- Morell Notes
Wound healing for a person on glucocorticoids improved with:
a) Vit A
b) Vit K
c) Vit B12
d) Vit C
Answer: Vitamin A
Corticosteroids inhibit inflamm. phase of wound healing (angiogenesis, neutrophil and macrophage migration and fibroblast proliferation) and therefore reduce collagen synthesis and wound strength. Steriods also inhibit epithelization and contraction and increased risk of wound infection (immunosupressive effect). Attempt should be made to avoid for 3-4 days post-op ot alternatively use steriod with less anti-inflammatory action. Vit A (topical) can help by stimulating collagen synthesis and promote epithelization. - Schwartz 2005
Levenson and Demetrio recommend vitamin A supplementation of 25,000 IU daily before and after elective surgery. (14) Research supports perioperative vitamin A supplementation in patients known to be immune depleted or steroid treated. Surgical patients with sepsis and those with fractures, tendon damage, or vitamin A deficiency may also benefit from perioperative vitamin A supplementation. Additional research is necessary to establish the effectiveness of universal perioperative vitamin A supplementation in healthy individuals
- http://findarticles.com/p/articles/mi_m0FDN/is_4_8/ai_111303980/pg_3
Corticosteroids blunt the processes of the entire inflammatory phase. Vitamin A (topically or 25,000 IU/d orally) mitigates the detrimental healing effects of corticosteroids, but hepatotoxicity may result from prolonged use (ie, >1 mo). Nonsteroidal antiinflammatory medications (NSAIDs) also interfere with arachidonic acid metabolism and, therefore, wound healing. Additionally, NSAIDs inhibit platelet function, one of the earliest processes in the inflammatory phase.
- http://emedicine.medscape.com/article/1298452-overview
Oncotic pressures between intravascular and extravascular compartments is best determined by?
a) Intravascular Na
b) Extravascular Na
c) Intravascular protein
d) Extravascular protein
Answer: Intravascular protein
Oncotic = protein Osmotic = Na
Because the capillary barrier is readily permeable to ions, the osmotic pressure within the capillary is principally determined by plasma proteins that are relatively impermeable. Therefore, instead of speaking of “osmotic” pressure, this pressure is referred to as the “oncotic” pressure or “colloid osmotic” pressure because it is generated by colloids. Albumin generates about 70% of the oncotic pressure. This pressure is typically 25-30 mmHg. The oncotic pressure increases along the length of the capillary, particularly in capillaries having high net filtration (e.g., in renal glomerular capillaries), because the filtering fluid leaves behind proteins leading to an increase in protein concentration.
- http://www.cvphysiology.com/Microcirculation/M012.htm
What would you use to resuscitate a child with pyloric stenosis?
In cases of clinical dehydration, children with pyloric stenosis require rehydration with IV fluid therapy before surgery. Administer D5W with 0.45% NaCl IV at 1.5 times the maintenance rate. Severely dehydrated children should receive initial deficit fluid therapy with 0.9% NaCl.When urine output is demonstrated, KCl 10-20 mEq/L can be added to the fluids.
Answer: D51/2NS at 16cc/hr or with 20kcl at 25cc/hr
The preoperative treatment is directed toward correcting the fluid, acid-base, and electrolyte losses. Intravenous fluid therapy is begun with 0.45-0.9% saline, in 5-10% dextrose, with the addition of potassium chloride in concentrations of 30-50 mEq/L. Fluid therapy should be continued until the infant is rehydrated and the serum bicarbonate concentration is less than 30 mEq/dL, which implies that the alkalosis has been corrected
Appropriate fluid therapy in this situation requires maintenance in addition to replacement for estimated deficit and for ongoing losses. Estimated initial volume replacement for the first 24 hours includes maintenance of 100 cc/kg (4 cc/kg/hr) = 400cc/24hrs or 16cc/hr and replacement of approximately half of the estimated deficit (from chart above = approx 90cc/kg = 360 cc/2 = 180/24hrs = 7.5cc/hr) → 16cc/hr + 7.5cc/hr = approx 25cc/hr
As far as electrolytes are concerned, sodium, potassium, chloride must be supplied for both maintenance and replacement of gastric losses. They can be supplied by a solution of 5% dextrose with 0.5% NS and KCl ( 20-30 mEq/L)
Pediatric patient with non bilious vomiting. An olive mass in abdominal exam what would be the electrolyte abnormality:
a. Low K, Low Cl, metabolic alkalosis
b. Low K, Low Cl, metabolic acidosis
c. Hi K, low Cl, metabolic acidosis
d. Low K, hi Cl metabolic alkalosis
Answer: Low K, Low Cl, metabolic alkalosis
Paradoxically urine is acid because K is so depleted that kidney shifts to H+ excretion.
Pyloric Stenosis: marked hypertrophy and hyperplasia of the 2 muscular layers of the pylorus occur….leads to narrowing of gastric antrum . The pyloric canal becomes lengthened, and the whole pylorus becomes thickened. The mucosa usually is edematous and thickened. Mutifactoral etiology but theorized that deficiency of nitric oxide synthase containing neurons, abnormal mysenteric plexus innervation, infantile hypergastrinemia, and exposure to macrolide antibiotics. History will reveal nonbilious vomiting or regurg. Which may become projectile (up to 70%). Emesis can be brown or coffee colour due to gastritis or MW tear at gastroesophageal junction. P/E 60-80% infants will have firm nontender and mobile hard pylorus 1-2 cm in diameter (“olive”) in RUQ at the lateral edge of rectus abdominus. Can become significantly dehydrated. Labs: hypochloremic, hypokalemic metabolic alkalosis. Persistent emesis causes progressive loss of fluids rich in hydrochloric acid, which causes the kidneys to retain H+ ions in favor of potassium. May also have elevated unconjugated bilirubin.
Paradoxic acid urea.
A 6 week old male is seen in the ER with a history of projectile vomiting for the previous 48 hours. He had weighed 4 kg last week when he was seen at his well baby check. Now the child weighs, 3.6kg and has a flattened anterior fontanelle. On abdo exam, a palpable olive sized mass is detected in the right of midline in the RUQ.
A capillary gas and electrolytes are ordered the most likely pattern would be:
Na K Cl HCO3
a. 135 3.5 103 14
b 135 3.0 95 20
c. 130 2.5 88 28
d. 135 2.5 112 30
e. 135 2.0 90 20
Child with pyloric stenosis, vomiting X 10 days, most likely electrolytes given four options with Na/Cl/K/Bicarb
Answer: c. 130 2.5 88 28
Eventually the infant will develop a nearly complete obstruction by
the second to fourth week of life, and will not be able to hold down even clear liquids. This invariably proceeds to severe dehydration if not treated. These infants develop a metabolic alkalosis with severe depletion of potassium and chloride ions. The serum pH level is high, whereas the urine pH level is high initially but eventually drops as the severe potassium deficit leaves only hydrogen ions to exchange with sodium ions in the distal tubule of the kidney.
- Schwartz chp37
In gastric losses, loss of Na, Cl, K, but not bicarb
When you administer 1L of normal saline you:
a) distribute equally the volume between all compartments
b) pull fluid from the extravascular space intravascularly
c) increase intravascular volume
d) increase intracellular volume
Answer: increase intravascular volume (?)
- NS will stay extracellular, approx ¾ interstitial and ¼ intravascular.
- NS does not go into the ICF
- Dextrose is distributed evenly among all compartments
- Plasma protein solutions stay intravascular
1L of RL will increase intravascular volume by:
a. 1L
b. 500cc
c. 250cc
d. 100cc
25% of RL or NS will go intravascular
What is the daily fluid requirement for a 8 kg infant?
a) 400 cc
b) 500 cc
c) 800 cc
d) 1000cc
e) 1200 cc
4x8 = 32 cc/h x24h= 768 cc
800c (based on 100/50/20)
Weight (kg) Fluid requirement (ml/d)
0 – 10 150/kg
10 – 20 1000 + 50/kg over 10
> 20 1500 + 20/kg over 20
- Kliegman: Nelson Textbook of Pediatrics, 18th ed.
- Bope: Conn’s Current Therapy 2010, 1st ed.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
Daily maintenance fluids can be calculated by the formula: 100 mL/kg up to 10 kg, add 50 mL/kg for 11 to 20 kg, and add 25 mL/kg for each kilogram of weight thereafter. Because I.V. fluid orders are written as milliliters per hour, this can be conveniently converted to 4 mL/kg/h up to 10 kg, add 2 mL/kg/h for 11 to 20 kg, and add 1 mL/kg/h for each additional kilogram.
- Schwartz
Calculation of Maintenance Fluid Requirements for Pediatric Patients
Weight (kg) Hourly Fluid Requirements (mL)
20 60 mL + 1 mL/kg for each kilogram above 20
Miller: Miller’s Anesthesia, 7th ed.
What rate should you bolus a child:
a) 10 ml / kg
b) 20 ml / kg
c) 30 ml / kg
d) 40 ml / kg
Restore cardiovascular stability with a rapid bolus of 20mL/kg over 10 to 30minutes
- Bope: Conn’s Current Therapy 2010, 1st ed.
The child is given a fluid bolus, usually 20 mL/kg of the isotonic fluid, over approximately 20 min.
- Kliegman: Nelson Textbook of Pediatrics, 18th ed.
The most water content can be seen in:
a) 60 y old man
c) 60 y old woman
a)
A 6 year old child presents with 25% dehydration. The FIRST clinical sign you would expect to see is: A. Tachycardia B. Hypotension C. Decreased urinary output D. Moist mucus membranes
C. Decreased urinary output
Strange question … at 25% dehydration all signs would be present. The first sign in mild is decreased urine output.
Point of this question is that children have large reserve. Minimal HD instability until they are really sick.
Of the findings on physical examination, the least accurate are mental status, heart rate, and fontanelle appearance.
Clinical Evaluation of Dehydration
Mild dehydration (1.5 sec); cool and pale
Severe dehydration (>10% in an infant; >6% in an older child or adult): rapid and weak or absent peripheral pulses; decreased blood pressure; no urine output; very sunken eyes and fontanel; no tears; parched mucous membranes; delayed elasticity (poor skin turgor); very delayed capillary refill (>3 sec); cold and mottled; limp, depressed consciousness
- Kliegman: Nelson Textbook of Pediatrics, 18th ed.
All of the following are in Ringer’s Lactate except:
a) Na – 130
b) Cl – 109
c) K – 4
d) Ca – 9
e) Lactate – 28
1) Ca 9
Na 130 K 4 Ca 2.7 Cl 109 HCO3 28 Osm 273
Which of the following has the highest sodium content? A – ringers lactate B - Extra cellular fluid C – D5W D – Ringers lactate
B - Extra cellular fluid
NS & D5NS > ECF > RL > D5½NS > 2/3 1/3
Major intracellular cations
a. Na + Ca
b. K + Mg
c. PO and protein
d. Cl and HCO3
b. K + Mg
Intracellular Cations: K+ 150, Mg+ 40, Na+ 10
Intracellular Anions: Protein 40, HPO4/SO4 150, HCO3 10
Extracellular Cations: Na+ 144, K+ 4, Mg++ 2, Ca++ 3
Extracellular Anions: Cl- 114, HCO3 30, SO4/PO4 3, Organic Acids 5, Protein 1
what is the plasma volume of 70kg male patient: = 3.5L
a. 3L
b. 4L
c. 2L
d. 2.5L
About 55% of whole blood is blood plasma, a fluid that is the blood’s liquid medium, which by itself is straw-yellow in color. The blood plasma volume totals of 2.7–3.0 litres (2.8–3.2 quarts) in an average human.
- http://en.wikipedia.org/wiki/Blood#Plasma
TBW = 0.60 x male weight, = 0.50 x young female weight ECF = 1/3 of TBW, plasma is ¼ of this, ¾ is interstitial/lymphatic. Plasma represents 8% of TBW and 5% of body weight. ICF = 2/3 of TBW
(Based on standard calculations, plasma for a 70kg male would be 3.5L)
Which is important for collagen production a – Vitamin A b – Vitamin B c – Vitamin C d – Vitamin E
Answer: Vitamin C
Requried for both hydroxylation of proline and lysine
When looking at the structure of collagen all are true except:
a) presence of hydroxyproline
b) presence of hydroxyserine
c) have a triple helix of three polypeptide alpha chains
d) have a gly-x-y repeating sequence
Answer: hydroxyserine
Each collagen is composed of three chains that form a trimer in the shape of a triple helix. The polypeptide is characterized by a repeating sequence in which glycine is in every third position (Gly-X-Y, in which X and Y can be any amino acid other than cysteine or tryptophan), and it contains the specialized amino acids 4-hydroxyproline and hydroxylysine.
- Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed.
Lysyl oxidase is an extracellular copper enzyme that catalyzes formation of aldehydes from lysine residues in collagen and elastin precursors.[3][4] These aldehydes are highly reactive, and undergo spontaneous chemical reactions with other lysyl oxidase-derived aldehyde residues, or with unmodified lysine residues. This results in cross-linking collagen and elastin, which is essential for stabilization of collagen fibrils and for the integrity and elasticity of mature elastin.
- http://en.wikipedia.org/wiki/Lysyl_oxidase
Collagen I:III ratio is :
a. 4:1
b. 8:1
c. 28:1
d. 36:1
e. 1:1
a. 4:1
I: 80-85%
III: 10-15%
What contains a high percentage of Type 2 collagen:
a. Bone
b. Cartilage
c. Basement membrane
b. Cartilage
COMMON TYPES OF COLLAGEN
Type Tissue Distribution
I Skin, bone, tendon, organ capsules, arteries (not cartilage)
II Cartilage, vitreous humor
III Skin, vessels, uterus. Usually found with
type I (type III collagen is the initial one in scars)
IV Basement membranes
V Widespread
VII Fibrils that anchor epidermis to dermis
VIII Cornea, vessels
IX, XI Hyaline cartillage
- Goldman: Cecil Medicine, 23rd ed.
Types 2, 9, 10, and 11 collagens are important structural components of hyaline cartilage.
- Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed
2) In collagen synthesis the proline and lysine are hydroxylated. The cofactors involved include all EXCEPT
a. ferrous iron
b. alpha-ketoglutarate
c. ascorbic acid
d. oxygen
e. zinc
e. zinc - not required for collagen hydroxylation but is required for collagen synthesis
a. ferrous iron (yes)
b. alpha-ketoglutarate (yes)
c. ascorbic acid (yes)
d. oxygen (yes)
TGF-beta is a potent inducer of extracellular matrix production, stimulating the synthesis of collagen types I, II, and V, fibronectin, and glycosaminoglycans.
The collagen molecule has abundant quantities of two unique amino acids, hydroxyproline and hydroxylysine. The hydroxylation process that forms these amino acids requires ascorbic acid (vitamin C) and is necessary for the subsequent stabilization and cross-linkage of collagen.
Collagen synthesis:
- stimulated by ascorbic acid, TGF-beta, IGF-1, and IGF-2.
- Required cofactors/coenzymes (4): ferrous Fe, -ketoglutarate, ascorbic acid (vitamin c), and oxygen cofactors.
(Morell Notes)
Vitamin C, zinc, iron, and copper are all enzyme co-factors in collagen synthesis.
- Duthie: Practice of Geriatrics, 4th ed.
Amino acid in the urine indicative of collagen breakdown a- methrmine b- cystine c- hydroxyproline d- histadine e- praline
Answer: hydroxyproline
Proline and hydroxyproline are found in high concentrations in collagen. Neither of these amino acids is normally found in urine in the free form except in early infancy. Excretion of “bound” hydroxyproline (dipeptides and tripeptides containing hydroxyproline) reflects collagen turnover and is increased in disorders of accelerated collagen turnover, such as rickets or hyperparathyroidism.
- Kliegman: Nelson Textbook of Pediatrics, 18th ed.
What is the rate limiting step in collagen synthesis?
a) Hydroxylation of proline
b) Procollagen conversion to collagen
c) Extravasation of collagen from the fibroblast
d) Uptake of proline
Proline hydroxylation is a rate-limiting step in collagen synthesis by dermal cells;
- Townsend: Sabiston Textbook of Surgery, 18th ed.
Vitamin C has been shown unequivocally to have a major role in wound healing. The major site of action is thought to be:
A. Glycosylation of hydroxylysine
B. Polymerization and formation of covalent bonds
C. Hydroxylation
D. Co-factor for procollagen peptidase
Answer: hydroxylation of proline to hydroxyproline
Ascorbic acid functions in a variety of biosynthetic pathways by accelerating hydroxylation and amidation reactions. The best-established function of vitamin C is the activation of prolyl and lysyl hydroxylases from inactive precursors, providing for hydroxylation of procollagen.
- Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed.
If you don’t have vit C the chains are defective = scurvy
The biochemical function of vitamin C is well known, and secondary functions relating to collagen gene expression have also been described. As mentioned in the discussion of collagen metabolism, ascorbate is a cofactor in the hydroxylation of proline to form the amino acid hydroxyproline during the synthesis of collagen. Ascorbate is essential for the addition of molecular oxygen to form the hydroxyl group of hydroxyproline. In human beings, thermally unstable collagen is produced if dietary ascorbate is insufficient. Old healed wounds thus tend to disrupt preferentially compared with the normal surrounding skin for two reasons. First, the scar is never as strong as surrounding skin. Second, there is more collagenase activity in normal scar tissue than in normal skin.
- Schwartz 2000
MHC class 1 antigen:
a. stimulate helper T cells
b. interact with cytotoxic T cells
c. Suppress helper T cells
d. All of the above
e. None of the above
Answer: target cytotoxic T cells
cytotoxic t-cells CD8 (MHC1)
helper T-cells CD4 (MHC2)
Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells since they express the CD8 glycoprotein at their surface. These cells recognize their targets by binding to antigen associated with MHC class I, which is present on the surface of nearly every cell of the body. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules that are expressed on the surface of Antigen Presenting Cells (APCs). - http://en.wikipedia.org/wiki/T_cell
The function of MHC class II gene products appears to be to regulate the specificity of helper T cells, which, in turn, regulate delayed-type hypersensitivity and antibody response to foreign antigens. - Bradley: Neurology in Clinical Practice, 5th ed.
MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other one being simply MHC class II) and are found on every nucleated cell of the body (and thus not on red blood cells though paradoxically are found on platelets). Their function is to display fragments of proteins from within the cell to T cells; healthy cells will be ignored while cells containing foreign proteins will be attacked by the immune system. - http://en.wikipedia.org/wiki/MHC_class_I
MHC I – Tc (CD8+)
MHC II – Th (CD4+)
T cells are the principal orchestrators of
a. hyperacute transplant rejection
b. the arthus reaction
c. immediate cytotoxic hypersensitivity
d. contact delayed hypersensitivity
Based on below, T cells are involved in:
- hyperacute transplant rejection (but mostly IgG antibodies)
- acute cellular rejection
- contact delayed hypersensitivity
Hyperacute rejection is a rare and preventable cause of primary graft nonfunction. It is caused by unrecognized ABO incompatibility or a positive T cell crossmatch (mediated by anti-HLA class I antibodies), both of which are contraindications to kidney transplantation. The diagnosis of hyperacute rejection is usually made by the surgeon in the operating room, as the pink kidney becomes mottled and cyanotic. There is little or no urine output and no renal blood flow by renal scan or duplex Doppler. There is no effective therapy, although plasmapheresis has been tried in uncontrolled reports. Transplant nephrectomy is the usual outcome. - Brenner & Rector's The Kidney, 6th ed.
Immune complexes may form locally within solid tissue at sites of high antigen concentration. Autoimmune thyroiditis and Goodpasture’s syndrome are examples of such localized immune complex formation called the Arthus reaction. It is generally agreed that the local Arthus lesion is one model of immune complex vasculitis in humans that is also due to the interactions of neutrophils with immune complexes and complement..
- Goldman: Cecil Textbook of Medicine, 21st ed.
Acute cellular rejection is most commonly seen within the initial months after transplantation and is heralded by clinical and biochemical signs of renal failure. Histologically, there may be extensive interstitial mononuclear cell infiltration and edema as well as mild interstitial hemorrhage ( Fig. 6-40B ). As might be expected, immunohistochemical staining reveals both CD4+ and CD8+ T lymphocytes, which express markers of activated T cells, such as the α chain of the IL-2 receptor
- Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed.
Contact dermatitis is a common example of tissue injury resulting from delayed hypersensitivity. It is evoked by coming in contact with urshiol, the antigenic component of poison ivy or poison oak, and manifests in the form of a vesicular dermatitis (Fig. 7-18) . The basic mechanism is similar to that described for tuberculin sensitivity. On re-exposure to the plants, the sensitized CD4+ cells of the TH 1 type first accumulate in the dermis, then migrate toward the antigen within the epidermis. Here they release cytokines that damage keratinocytes, causing separation of these cells and formation of an intraepidermal vesicle (Fig. 7-18) . In this form of delayed hypersensitivity, there is evidence that, in addition to CD4+ cells, some CD8+ cells may also be involved. In certain other forms of delayed hypersensitivity reactions, especially those that follow viral infections, cytokine-producing CD8+ cells may be the dominant effector cells.
- Robbins
Hyperacute rejection is a complement-mediated response in recipients with pre-existing antibodies to the donor (for example, ABO blood type antibodies)
Acute rejection […] is caused by mismatched HLA, which are present on all cells of the body.
[Chronic] rejection is […] where the rejection is due to a poorly understood chronic inflammatory and immune response against the transplanted tissue.
- http://en.wikipedia.org/wiki/Transplant_rejection
1) The cellular response to stress is best characterized by which of the following terms?
a. Hypertrophy
b. Metaplasia
c. Atrophy
d. Hyperplasia
e. Neoplasia
??
Adaptations are reversible functional and structural responses to more severe physiologic stresses and some pathologic stimuli, during which new but altered steady states are achieved, allowing the cell to survive and continue to function. The adaptive response may consist of an increase in the size of cells (hypertrophy) and functional activity, an increase in their number (hyperplasia), a decrease in the size and metabolic activity of cells (atrophy), or a change in the phenotype of cells (metaplasia). When the stress is eliminated the cell can recover to its original state without having suffered any harmful consequences.
Dysplasia – a loss in the uniformity of individual cells as well as a loss in their architechtural orientation. This is usually referred to as a premalignant lesion, however not all dysplasias progress to cancer.
Metaplasia- reversible change in which one adult cell type is replaced by another. May be in response to stress.
Examples – smokers, columnar to squamous metaplasia in respiratory tract. Here the most frequent cancer is squamous cell carcinoma.
Barrett’s oesophagitis – squamous oesophageal lining is replaced by hardier intestinal cells often giving rise to dysplasia and adenocarcinoma.
- Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed
Apoptosis is best defined by:
Apoptosis is the process of programmed cell death or cell suicide.
All of the following are true except:
a. Necrosis is a non controlled process that leads to stimulation of inflammation
b. Apoptosis is important for tissue growth
c. Both necrosis and apoptosis happen in perfusion injury
d. Initiated by Golgi bodie
Answer: Initiated by Golgi bodie
Golgi body protects from apoptosis
Apoptosis is controlled, necrosis isn’t
The Golgi has a putative (assumed) role in apoptosis, with several Bcl-2 family members localised there, as well as to the mitochondria. A newly characterised protein, GAAP (Golgi anti-apoptotic protein), almost exclusively resides in the Golgi and protects* cells from apoptosis by an as-yet undefined mechanism
In adult tissues the size of cell populations is determined by the rates of cell proliferation, differentiation, and death by apoptosis and increased cell numbers may result from either increased proliferation or decreased cell death.[5] Apoptosis is a physiologic process required for tissue homeostasis, but it can also be induced by a variety of pathologic stimuli.
- Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed.
In many clinical situations (e.g., hypovolemic shock, suprarenal aortic-cross clamping) the kidney is subject to a classic ischemia-reperfusion injury that involves several distinct phases.[80] Acute injury to the tubular epithelium and vascular endothelium initiates a rapid decline in GFR. The injury is extended by epithelial and endothelial cell apoptosis and necrosis.
- Miller: Miller’s Anesthesia, 7th ed
Which statement is not true
a) necrosis occurs due to exogenous forces
b) apoptosis is programmed cell death
c) necrosis had minimal effect on surrounding tissues
d) necrosis involves cell swelling and protein coagulation
e) apoptosis involves cell shrinking and chromatin condensation
c) necrosis had minimal effect on surrounding tissues
Necrosis is caused by either physical or chemical damage. The cell loses its ability to regulate osmotic pressure and the cell explodes. Apoptosis the cell shrinks and there is Nuclear and cytoplasmic condensation. The main morphological characteristics of apoptosis are nuclear fragmentation and cellular breakdown into apoptotic vesicles. In contrast to necrosis, there is no release of cellular contents in the interstitium, and therefore no inflammation surrounding the cell death. Internucleosomal DNA fragmentation (without any sequence specificity but probably more intense in chromatin in the “open configuration”) is another important biochemical feature that is the result of an endonuclease activity that has not yet been isolated (Gerschenson & Rotello, 1992). Apoptosis differs from necrosis because necrosis is a degenerative phenomenon of a group of cells that follows irreversible injury. Necrosis is a progressive dissolution of cell structure always accompanied by random DNA degradation.
Regarding cartilage what is true:
a. Axial pressure has no effect on cartilage thickness.
b. Cartilage has no blood vessels but has innervation.
c. No nerves or blood vessels.
d. Cartilage has both blood vessels and innervation
c. No nerves or blood vessels.
Articular cartilage has a very limited capacity for self repair. Small damage does not repair itself and can often get worse over time. As cartilage is aneural and avascular (does not have nerve supply), shallow damage often does not trigger pain.
- http://en.wikipedia.org/wiki/Articular_cartilage_damage
Which of the following is a counterregulatory hormone?
a. insulin
b. catecholamines
c. somatostatin
d. cytokines
Answer: catecholamines
According to below, cytokines as well
A counterregulatory hormone is a hormone that opposes the action of another.
Nutrition and Metabolic Control - Key Points
- Sepsis, trauma, and surgery activate complex metabolic and inflammatory responses that affect all body systems.
- The metabolic response to stress response is characterized by catabolism, hypermetabolism, hyperglycemia (diabetes of injury), and enhanced lipolysis.
- The counterregulatory hormones (cortisol, glucagon, catecholamines) along with the cytokines (e.g., IL-1, TNF) are major mediators of this response.
- Miller: Miller’s Anesthesia, 7th ed.
All of the following are considered to be a part of the group of substances called cytokines EXCEPT?
a) platelet activating factor
b) colony stimulating factor
c) interleukin-1
d) tumor necrosis factor
Answer: platelet activating factor
Immune responses are regulated by soluble mediators called cytokines that produce a multiplicity of immune events through interactions with appropriate cytokine receptors on tissue and inflammatory cells. Cytokines serve an important role as messengers within the immune system and in conjunction with the rest of the body to regulate immune responses.
Colony stimulating factor is secreted by macrophages to help undifferentiated hematopoetic cells differentiate (WBC)
Specificy of antibody for antigen:
a) Fc portion of the long chain
b) Variable regions of the short and long chains
c) Fixed regions of the short and long chains
d) Variable region of the short and fixed region of the long chain
e) Fixed region of the short and varied region of the long chain
b) Variable regions of the short and long chains
Basically the antibody is shaped pretty standardly, except the ends of them that are variable to recognize different antigens
The fragment antigen-binding (Fab fragment) is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. These domains shape the paratope — the antigen-binding site — at the amino terminal end of the monomer.
- http://en.wikipedia.org/wiki/Fragment_antigen-binding
This variable region, composed of 110-130 amino acids, give the antibody its specificity for binding antigen. The variable region includes the ends of the light and heavy chains.
- http://www.biology.arizona.edu/immunology/
tutorials/antibody/structure.html
70kg male what is protein requirement to prevent protein catabolism
a) 50g,
b) 100g
c) 200g
d) 500g
1) 50g
Recommended Daily Protein Intake
Normal conditions = 0.75g/kg/day = 52.5g (also seen 0.5g/kf/day)
Metabolic stress = 1.0-1.6g/kg/day = 75g to 112g
[T]he average normal requirement is 0.8 g of protein per kilogram, or between 56 and 60 g of protein per day. Trauma, infection, and other catabolic conditions will increase this requirement.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
A healthy 70 kg man with intact protein stores requires approximately how many grams of protein per day (gm/kg) in his oral diet to maintain adequate protein stores?
a. 0.8 gm/kg (56 gm/day)
b. 2.0 gm/kg (140 gm/day)
c. 3.8 gm/kg (266 gm/day)
d. 4. gm/kg (280 gm/day)
e. None of the above.
a. 0.8 gm/kg (56 gm/day)
The extensive studies of whole body protein turnover by Graham Hill and Robert Wolfe during the 1980s documented that exogenous protein administration of 1.5 g/kg/day achieves maximal protein sparing and that when amounts exceeding this value are administered, no further incorporation of nitrogen into protein is possible, with the excess protein being converted to urea and excreted, at least in relatively normal patients. Accordingly, it is most common to administer protein during artificial nutrition, whether enteral or parenteral, at a value of 1.5 g/kg/day. It is not clear in patients with severe protein loss, such as after major burns, whether limiting protein intake to this level is efficacious, and many centers have attempted to administer even greater amounts of protein (e.g., 2 g/day) to correct measured deficits.
- Townsend: Sabiston Textbook of Surgery, 18th ed.
Daily turnover of protein in an 80Kg man is a-1% b-3% c-5% d-9%
Answer: 3%
A 70-kg man has between 10 and 11 kg of protein, otherwise referred to as lean body mass. In the fed state, daily protein turnover amounts to between 250 and 300 g, or 3%.
The average normal requirement is 0.8 g of protein per kilogram, or between 56 and 60 g of protein per day. Trauma, infection, and other catabolic conditions will increase this requirement.
Exogenous protein administration of 1.5 g/kg/day achieves maximal protein sparing and that when amounts exceeding this value are administered, no further incorporation of nitrogen into protein is possible
- Townsend: Sabiston Textbook of Surgery, 18th ed.
1) Caloric : nitrogen ratio in trauma patient
a. 100:1
b. 150:1
c. 200:1
d. 300:1
1) 100:1
Increased protein intake, and a therefore a lower calorie:nitrogen ratio 80:1-100:1 may benefit healing in critically ill or hypermetabolic patients
- Schwartz
Normal = 150:1
Severe stress = 80-120:1
A patient has renal insufficiency and requires nutritional support. Which of the following is the BEST recommendation?
A. Lower the caloric/ nitrogen ratio
B. Increase the caloric / nitrogen ratio
C. Avoid branched chain amino acids
D. Recommend an alternate source of calories other than glucose
B. Increase the caloric / nitrogen ratio
Want less protein, cause they don’t pee out excess nitrogen in the form of urea as well
What are the minimum requirements for carbohydrates for an adult?
Answer provided: 100-500g/day
Glucose administration during fasting or stress appears to decrease urinary urea production, the so-called protein-sparing effect, with a minimum of 100 g of glucose per 24 hours being required for this response based on Gamble’s classic lifeboat ration studies of the 1940s.
Maximum suppression of gluconeogenesis is achieved at infusion rates of 4 mg/kg/min (∼400 g/day for a 70-kg man)
- Townsend: Sabiston Textbook of Surgery, 18th ed.
A starvation state is characterized by the following except:
a) Negative nitrogen balance
b) Increased urine urea
c) Increased liver albumin production
d) Decreased uptake of lactate by liver
c) Increased liver albumin production
Just think of all your patients and how they all have hypoalbuminemia
Decreased albumin is associated with the following conditions:
Starvation, malnutrition, malabsorption, anorexia (decreased synthesis)
The liver is the principal organ that maintains total carbohydrate stores by synthesizing glycogen and generating glucose from precursors.[85] Glucose is synthesized from nonoxidative metabolic products of glucose (pyruvate and lactate) that are generated predominantly by red blood cells (RBCs) and from amino acid precursors that are derived predominantly from muscle during prolonged starvation or exercise.
- Feldman: Sleisenger & Fordtran’s Gastrointestinal and Liver Disease, 8th ed.
Which of the following will you NOT find in a state of prolonged starvation?
a. dec basic metabolic rate
b. dec. cardiac output
c. hypoglycemia
d. increased urea
e. increased free fat acid and ketoeamia in plasma
d. increased urea
What happens to urea, during acute and prolonged starvation?
Acute – Nitrogen breakdown 8-12 g/day b/c high gluconeogeneis from aa breakdown; excreted in urine as urea
Chronic – Ketogenesis inhibts gluconeogenesis, thus nitrogen breakdown 2-3g/day; excreted as ammonia (not urea) b/c ammonia counters the acidosis from ketosis
A maximal rate of ketogenesis is reached by 3 days of starvation, and plasma ketone body concentration is increased 75-fold by 7 days.
Muscle protein breakdown decreases to less than 30 g/day, causing a marked decrease in urea nitrogen pro-duction and excretion.
- Feldman: Sleisenger & Fordtran’s Gastrointestinal and Liver Disease, 8th ed
Heart size and cardiac output are reduced, the pulse slows, and blood pressure falls.
- Auerbach: Wilderness Medicine, 5th ed.
