6/21 Flashcards
image of RGPN
crescent moon shape on LM and IF
crescents are made of fibrin and plasma proteins (C3b)
how are NPV and disease prevalence related?
inversely proportional-
as disease prevalence (or pretest probability) increases, NPV decreases
describe biochemistry and phenotype of PKU
due to low Phenylalanine hydroxylase (or low BH4)
cannot convert phenylalanine to tyrosine, so tyrosine becomes essential
need to avoid aspartame (contains phenylalanine–> accumulation)
symtoms arise if you let phenylalanine accumulate:
- MUSTY BODY ODOR, seizures, fair skin/hypopigmentation, intellectual disability, growth problems
- excess phenylketones in urine
–need to test 2-3 days after birth to rule out protective maternal enzymes
which disorder is associated with characteristic tennis racquet organelles?
Langerhans histiocytosis
AKA birbeck granules
Langerhans cells normally are the most abundant APCs in skin and mucosa, and interact closely with T lymphocytes
In this disease, they’re immature and do not stimulate T cells via antigen presentation.
describe Kupffer cells
specialized macrophages in liver sinusoid lining
describe inflammatory breast cancer
peau d’ orange
erythematous, itchy, textured rash
causes obstruction to lymph nodes (LAD)
describe Paget disease of the breast
from underlying DCIS or invasive cancer
- non-healing ulcer w/ oozing
- eczema patches on nipple
contrast invasive ductal carcinoma from invasive lobular carcinoma
Invasive ductal carcinoma:
most common (75%)
-firm, rock-hard mass w/ sharp margins
-“stellate” infiltration
Invasive lobular carcinoma:
often bilateral w/ multiple lesions
-“indian file” row of cells due to low E-cadherin expression
describe secondary lactose intolerance
deficient/absent lactase
loctase normally hydrolyzes into glucose + galactose via lactase
Secondary lactose intolerance: acquired, due to inflammation (celiac) or infection (Giardiasis) –> cell damage to intestine; the replaced cells are lactase deficient
what disease process is associated with KRAS
KRAS mutation causes uncontrolled cell proliferation that increases adenoma sizes, increasing their likelihood of progressing to adenocarcinoma
colon, lung, and pancreatic cancer
the final mutation needed to turn into carcinoma is TP53
describe Tay Sachs disease
“Tay Sachs lacks hexosaminidase” A
Build up of GM2 ganglioside (–>GM3)
causes progressive neurodengeration, dev delay, “cherry red spot” on macula, onion skin lysosomes
NO HSM
“take a sack of 6 degenerated cherries and onions from from the GM gang on the side”
describe Niemann Pick Disease
“No man picks his nose with his sphinger”
deficient Sphingomyelinase
build up of sphingomyelin (–> ceramide)
progressive neurodegeneration, foam cells (lipid laden macrophages), cherry red spot on macula
HSM PRESENT
“No man “in his right mind” would pick MEGA foamy cherries”
describe fabry disease
lack of alpha-galactosidase A
build up of ceramide trihexoside (–> glucocerebroside)
early:
triad of episodic peripheral neuropathy, angiokeratomas in bathing trunk distribution, and hypohidrosis
late:
progressive renal failure, CVD
“bathing trunk fabric w/ mittens and socks”
describe Gaucher disease
most common lysosomal enzyme deficiency
deficient glucocerebrosidase (beta glucosidase)
treat: recombinant glucocerebrosidase
build up of glucocerebroside (–> ceramide)
HSM, pancytopenia, osteoporosis, aseptic necrosis of femur (erlenmeyer flask deformity- bone pain), bone crises, Gaucher cells (lipid laden macrophages resembling crumpled tissue paper), massive HSM, especially spleen
“massive grocery sack of pans, erlenmeyer flasks, and liver for dinner w/ side of glucocerebro”
describe krabbe disease
deficient galactocerebrosidase
build up of psychosis and galactocerebroside (–> ceramide)
peripheral neuropathy, developmental delay, optic atrophy, globoid cells
describe metachromatic leukodystrophy
deficient Arylsulfatase A
build up of cerebroside sulfate (–> glucocerebroside)
central and peripheral demyelination with ataxia, dementia
describe clinical significance of neurophysins
carrier proteins for oxytocin and ADH
carry to posterior pituitary
mutated neurophysins cause Diabetes Insipidus (insufficient ADH release)
describe statins and their side effects
HMG CoA reductase inhibitor
(inhibits mevalonate production)
primary effect is DECREASE IN LDL
can cause muscle and liver toxicity- check LFTs
describe terbinafine’s MOA and indication
inhibits squalene epoxidase fungal enzyme
-inhibits fungal membrane ergosterol synthesis
used for dermatophytoses
effect of carotid massage
vagal maneuver (also incl Valsalva, cold water immersion)
increase in parasympathetic tone
causes temporary inhibition of SA node –> prolonged AV node refractory period
useful in terminating paroxysmal supra ventricular tachycardia
describe OCPs
progestin/progesterone is responsible for pregnancy prevention in all hormone contraceptions.
Estrogen often improves bleeding
progestin can be local or systemic effect
combined OCPs: systemic effects via suppressing GnRH in hypothalamus (which decreases FSH and LH in anterior pituitary)
-no LH spike, so no ovulation
all progestin-containing contraceptives thin the uterine lining to impair implantation and thicken cervical mucus to prevent entry
equation for calculating half life
t(1/2) = (0.7 x Vd) / CL
what type of fracture and nerve injury is associated with a deep brachial injury
mid shaft fracture
radial nerve
when is the brachial artery injured
supracondylar fracture
pseudomonas is associated with what type of skin problem
ecthyma gangrenosum
skin patches w/ necrosis 2/2 lack of blood flow
what are the pseudomonas virulence factors
exotoxin A- protein synthesis inhibition
elastase- degrades elastin / vessel destruction
phospholipase C- degrades cellular membranes
pyocyanin- generates ROS
what is opsoclonus-myoclonus syndrome and what neoplasm is it associated with
“dancing eyes dancing feet”
associated with childhood neuroblastoma- most common adrenal medulla tumor in children
abdominal mass that CAN cross midline (vs Wilms tumor)
how does Ewing sarcoma present
malignant bone tumor in teenagers, esp long bones
may resemble acute osteomyelitis
how does Wilms tumor present
nephroblastoma in young children
presents w/ palpable flank mass
micro looks like primitive metanephric tissue
what occurs in the peripheral NS after nerve damage
Schwann cells sense axonal degeneration and begin to degrade their myelin, secrete cytokines and chemokine that recruit macrophages
the clearance of myelin debris and trophic factor secretion stimulates growth cone formation from proximal axons tump to facilitate nerve regeneration
what occurs in the central NS after nerve damage
macrophages/microglia are recruited slowly (BBB). oligodendrocytes that normally produce myelin become inactive/apoptose.
myelin debris removal is slowed (years) which suppresses axonal growth via myelin-associated inhibitory factors.
astrocytes also release inhibitory molecs and proliferate after injury forming a GLIAL SCAR that acts as a barrier to axon regeneration
Wallerian degeneration- axon degradation distal to site of injury
how does chronic granulomatous disease present
NADPH oxidase deficiency
decreased ROS, decreased oxidative burst needed for neutrophils
increased susceptibility to catalase positive organisms
no green/blue on diagnostic imaging tests
what is the hallmark of pulmonary fibrosis
decreased lung compliance- willingness to expand when a pressure is exerted
what is myeloperoxidase
a blue-green heme-based enzyme that is released from neutrophil azurophilic granules in pus/sputum of bacterial infections
it catalyzes chloride + H2O2–> bleach during phagocytic respiratory burst
describe selective IgA deficiency
immune deficiency that’s usually asymptomatic w. recurrent sinopulmonary and GI infections and/or autoimmune disease.
Can have anaphylaxis when given blood transfusion
describe leukocyte adhesion deficiency
poor leukocyte adherence and transmigration through vasculature
recurrent skin/mucosal infections
no pus formation
delayed umbilical cord detachment
persistent leukocytosis
defect in LFA-1 ingetgrin on phagocytes
CD18
function of IL-12
stimulates differentiation of “naive” T-helper cells into Th1
deficiency in IL-12 receptors leads to mycobacterial infections 2/2 inability to mount strong cell-mediated granulomatous response
tx w/ IFN-gamma
what does Laplace’s law tell you about lungs
given identical surface tension, a smaller sphere will collapse before a larger one without any surfactant contribution because there has to be more distending pressure
compare/contrast collagen and elastin
both: synthesized in large polypeptide non-polar AAs
collagen: many are hydroxylated
form disulfide bridges and triple helixes
elastin:
few are hydroxylated
Lysyl oxidase + Copper destroys cross-links involving lysine
contrast small cell vs squamous cell lung carcinoma’s paraneoplastic syndromes
small cell: SIADH- (ADH hyponatremia w/ euvolemia) Cushing (ACTH) Lambert-Eaton Cerebellar ataxia
Squamous cell:
Hypercalcemia (PTHrP)
chromogranin staining shows ___
neuroendocrine cell- small cell carcinoma
describe chronic lung transplant rejection
affects small airways, causing bronchiolitis obliterates
characterized by lymphocytic inflammation, fibrosis, and ultimately destruction of bronchioles
how are particles cleared throughout the resp tract?
mucociliary clearance happens in terminal bronchioles
distal to that, phagocytosis and alveolar macrophages use lysosomal degradation and pulm lymphatics
goblet cells end just before bronchioles begin
describe Pancoast tumor
squamous cell carcinoma
commonly presents w/ compressing adjacent structures from its superior sulcus tumor location
Horner syndrome: ptosis, miosis, anhidrosis, enophthalmos
Pain in ulnar nerve distribution
Superior Vena Cava syndrome (facial edema, JVD)
erosion of adjacent vertebral structures
how does room air compare to a patient’s ABG
higher pO2
lower pCO2
higher pH
how do air values change at high altitude
lower pO2 (92 vs 160)
you increase your Hct to increase your O₂ carrying capacity
PaO2 and SaO2 both remain low because they’re independent of Hgb concentration
Dissolved O₂ depends on pAO2 and solubility in blood
-when pAO2 decreases (at high altitude), both paO2 and O₂ dissolved in blood decrease
Bound O₂ depends on Hb saturation
SaO2 is independent of Hct
the degree of Hb O₂ saturation is determined by pAO2
-at sea level, Hb is close to fully saturated
-at altitude, pAO2 and SaO2 decrease
the increase in Hgb concentration allows you to carry normal O₂ amounts even though your pAO2 and SaO2 are decreased at altitude
which vessel supplies nasal mucosa and bleeds when removing a nasal polyp
sphenopalantine artery, a terminal branch of the maxillary artery, which comes from the external carotid artery
describe a patient presentation of staph aureus pneumonia
post-viral (Influenza) pt w/ salmon colored sputum
cavitary lesion
CYP 450 inhibitors
Macrolides (except azithro) Quinidine, Quinolones Gemfibrozil Avirs Ciprofloxacin Acute Alcohol Grapefruit Juice Isoniazid (INH) Amiodarone Sulfonamides Ketoconazole Cimetidine
MacQuin and his friend GemAvir cip alcohol acutely w/ Grapefruit juice and Ise, then A-S-K for cimetidine for their stomach ache
CYP 450 inducers
Nevirapine Carbamazepine Rifampin Barbiturates Phenytoin St. John's Wort Modafinil Chronic alcohol use Griseofulvin
Nevir drive your CAR up the RAMP through the BARBwire PHENce into St. John’s Woods. You’ll mo-dafinitely be chronically attached by Griszley bears
which pts should avoid loop diuretics and thiazides?
pts w/ an allergy to sulfa drugs, for example trimethoprim/sulfamethoxazole
what patients should you suspect Klebsiella pneumonia in?
upper cavitary lesion in pts w/ encapsulated GN rods
alcoholics, aspiration, and abscesses
lactose fermenter, urease positive, immotile, currant red jelly sputum
pathway of retinal artery occlusion
internal carotid
ophthalmic artery
retinal artery
painless unilateral blindness
which fetal vessel is which
umbilical vein is oxygenated
umbilical arteries are deoxygenated
ductus venosus bypasses portal circulation
ductus arteriosus bypasses lungs
in what setting are Aschoff bodies found?
interstitial myocardial granulomas found in rheumatic fever 2/2 bacterial endocarditis
also seen w/ Anitschkow cells- enlarged macrophages w/ ovoid, wavy, rodlike nuclei (like ribbons)
describe ANP and BNP
Atrial natriuretic peptide:
released from atrial myocytes in response to high blood vol/A pressure
increases cGMP–> vasodilation and decreased Na reabsorption at collecting tubule
promotes diuresis via constricting efferent and dilating afferent arterioles
contributes to “aldosterone escape” mech
BNP: brain released from ventricular myocytes in response to tension longer half life than ANP blood test to dx HF available as Nesiritide to tx HF
how does idiopathic pulmonary fibrosis present
honeycomb lung, esp in subpleura spaces
interstitial fibrosis w/ cystic air spaces
dry cough
distinguish between absolute and relative polycythemia/erythrocytosis
Relative = normal RBC mass
2/2 dehydration or excessive diuresis
Absolute = true increase in RBC mass
2/2 polycythemia vera, where all 3 cell lines increase (with low EPO levels)
(Primary erythrocytosis)
or 2/2 secondary erythrocytosis, where EPO could be produced by tumors or stimulated via hypoxia; only RBCs increase (nl WBC and plts)
(secondary)
MOA of fibrates
fibroses inhibit cholesterol 7-alpha-hydroxylase, which is supposed to catalyze synthesis of bile acids.
the jelly fish’s main goal is to up regulate LPL (lighthouses) to improve triglyceride (trident-yielding) clearance, and decrease hepatic VLDL secretion. it actives PPAR-alpha to induce HDL synthesis
main goal: lower TG
reduced bile acid production results in decreased cholesterol solubility in bile and favors formation of cholesterol gallstones.
big risk of gallstones and myopathies, esp with statins.
describe the GLUT transporters
GLUT-4 is insulin DEPENDENT
found on skeletal muscle and adipocytes
all others are insulin-independent
GLUT-1: RBCs, brain, cornea, placenta
GLUT-2: beta islet cells, liver, kidney, SI
GLUT-3: brain, placenta
GLUT-5: spermatocytes, GI tract
insulin response in oral vs IV glucose
there’s a greater insulin response w/ oral glucose (vs IV) because of things like glucagon-like-peptide 1 (GLP1) that are released after meals from gut, independent of blood glucose level and increased beta cell sensitivity to glucose
what 2 things build up in Vit B12 deficiency?
methylmalonic acid (cofactor in Methylmalonyl CoA mutase --> Succinyl CoA) which causes impaired myelin synthesis
Homocysteine (cofactor in Methionine synthase –> methionine)
which causes impaired DNA synthesis
pt will present with:
megaloblastic anemia and pancytopenia, both related to impaired DNA synthesis
subacute combined degeneration of dorsal columns (loss of proprioception/vibration, Romberg sign) and lateral cortical spinal tract (spastic muscle weakness, hyperreflexia)
discuss HMP shunt
AKA pentose phosphate pathway
occurs in cytoplasm
provides NADPH from abundantly available Glucose-6-Phosphate
no ATP is used/produced
requires G6PD as its rate limiting step!
sites:
lactating mammary glands, liver, adrenal cortex (sites of fatty acid/sterol synthesis), RBCs
the NADPH produced is necessary to keep glutathione reduced, which keeps free radicals and peroxides detoxified
describe G6PD deficiency
it prevents NADPH production via G6P + (NADP+)
without NADPH, you have free radical and peroxide toxicity
free radicals will cause oxidative damage, particularly to RBCs, causing hemolytic anemia
oxidative stress will also denature the Hgb, cause it to ppt, and form Heinz Bodies
the Heinz bodies will be phagocytized via splenic macrophages, and create Bite Cells
“Bite into some Heinz ketchup”
pneumonic for remembering blotting techniques
SNoW DRoP
Southern Blot = DNA
Northern Blot = RNA
Western Blot = Proteins
Southwestern Blot = DNA-binding proteins
distinguish DNA Pol I, Pol 3, Primase, Gyrase, Helicase, Ligase
DNA Pol 3: only on prokaryotes
elongates leading strand and lagging strand
uses 3’–>5’ exonuclease to proofread
DNA Pol 1: only on prokaryotes
elongates leading strand and lagging strand
ALSO uses 5’–>3’ exonuclease to remove RNA primer and replace w/ DNA (via 5’–>3’ polymerase activity)
Primase: makes RNA primer
Gyrase: AKA topoisomerase
removes supercoils/tension
Helicase: unzips DNA at template fork
Ligase: combines Okazaki fragments via phosphodiester bonds
distinguish ornithine transcarbamylase deficiency from orotic aciduria
OTC deficiency:
most common urea cycle deficiency
-hyperammonemia (body cannot eliminate ammonia)
-excess carbamoyl phosphate is shunted to orotic acid (pyrimidine synthesis pathway), so you have high elevated orotic acid
-carbamoyl phosphate + ornithine normally participate in urea cycle to make urea, but ornithine needs OTC transport protein to get into the mitochondria to form citrulline, eventually producing urea
-hyperammonemia!!
-Tx w/ very low protein diet so you don’t have excess NH3 formation
Orotic aciduria:
defect in UMP synthase causing:
inability to convert orotic acid to UMP (in the de novo pyrimidine synthesis pathway)
-MEGALOBLASTIC ANEMIA (2/2 impaired DNA synthesis)
-orotic acid in urine
-no hyperammonemia!!!
-Tx w/ UMP to bypass mutated enzyme
discuss Niacin deficiency
Pellagra- “3 D’s”
dermatitis (sun exposed areas)
diarrhea (GI atrophy)
dementia (neuro degeneration)
Vit B3 is essential for NAD
Vit B3 can come via dietary intake or synthesized via tryptophan
Pellagra can also be seen in carcinoid syndrome, prolonged INH therapy, or Hartnup disease (deficiency in neutral AA transporters)
discuss Alkaptonuria
deficient homogentisate oxidase in tyrosine –> fumarate to go to the TCA cycle
causes blue-black pigment-forming homogentistic acid to accumulate in tissue, esp CT and sclerae!
urine turns black in air
“tyrosine –> fumarate”
“black tires –> fumes”
discuss homocysteinuria
excess homocysteine, intellectual disability, osteoporosis, marfanoid habitus, kyphosis, lens subluxation, THROMBOTIC EVENTS and atherosclerosis
normally:
Homocysteine –> either of 2:
methionine
via methionine synthase + B12
cystathionine then to cysteine
via CBS + serine + B6
cysteine is now essential
tx w/ Vit B6 to “force” CBS activity
discuss conversion of glucose to fructose via sorbitol
polyol pathway:
Glucose –> sorbitol
via aldose reductase + NADPH
sorbitol –> Fructose
via Sorbitol dehydrogenase + NAD+
sorbitol cannot cross cell membranes
insufficient sorbitol dehydrogenase causes sorbitol accumulation, which can cause cataracts, retinopathy, and peripheral neuropathy, esp in pts w/ chronic hyperglycemia/DM
discuss cyanide poisoning
bright red w/o cyanosis
labs show lactic acidosis and narrowing of the venous-arterial PO2 gradient (inability of tissue to extract oxygen)
cyanide has high affinity for Ferric Iron (Fe3+), which inhibits cytochrome C oxidase in the mito
administer inhaled amyl nitrate to oxidize the ferrous iron (Fe2+) to ferric iron (Fe3+) , which generates an induced methemoglobin
methemoglobin can’t carry O₂ but has has high affinity for Cyanide; cyanide binds the Fe3+ rather than the mitochondrial cytochrome enzymes, diminishing the toxic effect
discuss Lynch Syndrome
AKA hereditary nonpolyposis colorectal cancer HNPCC
DNA mismatch repair mutation (MSH2 mutation)
progress to colorectal cancer
proximal colon ALWAYS involved
CEOS: colorectal endometrial ovarian skin
what are PT and PTT used to monitor, respectively
INR is used for following patients on Warfarin
- calculated from PT
- Warfarin is a Vit K antagonist (2,7,9,10 factors)
- decreases in these factors, esp Fact 7, prolongs PT in the extrinsic pathway
activated PTT is used to monitor unfractionated heparin, which primarily affects the intrinsic coagulation pathway
(Hep = PTT)
what are the indications for and possible side effects of Aspirin therapy
commonly used to prevent ischemic stroke in pts w/ TIA
it irreversibly inhibits COX enzymes
at low doses, it predominately inhibits COX-1 (preventing plt synthesis of Thromboxane-A2, which impairs plt aggregation and reduces vasoconstriction)
this leads to risk of GI bleed:
- inhibition of plt aggregation
- impairment of prostaglandin-dependent GI mucosal protection
PPIs can help protect GI bleed risks in Aspirin pts
what is the preference order for Na-binding strength with use dependence of Class 1 anti-arrhythmics
C > A > B
Flecainide flakes is clutching his jar of PB while he eats in bed next to his Propafenone
The Quinidine queen and procainamide king casually eat their PB
the Lidocaine lady and mexiletine Mexican are too concerned about lying to pay attention to their PB
what are side effects of using anthracycline chemotherapeutic agents?
drugs that end in -rubicin
form free radicals in myocardium; cumulative dose-related dilated cardiomyopathy
presents w/ L and R ventricular CHF
dilated cardiomyopathy via swelling of SR, then loss of cardiomyocytes (myofibrillar dropout)
discuss pernicious anemia
Vit B12 deficiency- destruction of gastric mucosa in body/fundus, destroying parietal cells (which normally secrete intrinsic factor and HCl)
presents w/ megaloblastic anemia, LE paresthesias, and fatigue
parietal cells found in upper glandular layer of stomach, just deep to columnar epithelial cells
no parietal cells means no IF, which is required for B12 absorption in jejunum and duodenum
what is CCK’s function
responsible for gallbladder contraction, increasing pancreatic enzyme secretion (via acinar cells), and decrease gastric emptying
produced by I cells in duodenum and jejunum in response to fatty acts and AAs
review LN drainage:
cervical = head/neck
hilar = lungs
mediastinal = trachea/esophagus
axillary - upper limb, breast, skin above umbilicus
celiac = liver, stomach, spleen, pancreas, upper duodenum
Superior mesenteric = lower duodenum, jejunum, ileum, colon to splenic flexure
inferior mesenteric = splenic flexure to upper rectum
internal iliac = lower rectum to anal canal (above pectinate line), bladder, vagina (middle third), cervix, prostate
para-aortic = testes, ovaries, kidneys, uterus
superficial inguinal = anal canal (below pectinate line), skin below umbilicus (except popliteal), scrotum, vulva
popliteal = dorsolateral foot, posterior calf
what’s the mnemonic for retroperitoneal structures
SAD PUCKER
Suprarenal (adrenal) glands Aorta and IVC Duodenum (2,3,4th) Pancreas (except tail) Ureters Colon (descending and ascending, NOT transverse) Kidneys Esophagus (thoracic) Rectum (partial)
what 2 areas are watershed areas in the abdomen?
splenic flexure and retrosigmoid junction
]they lie between regions of perfusion of major arteries
they’re particularly susceptible to ischemic damage 2/2 hypotension
what is the triple therapy for H pylori
PPI
amoxicillin
clarithromycin (macrolide)
what are the gene mutations for colon cancers?
MSH2- Lynch Syndrome/HNPCC
APC- FAP, sporadic colon cancer
VHL- VHL
p53- Li-Fraumeni syndrome
MEN1- MEN1
RET- MEN2
what are the risk factors for esophageal cancers?
Adenocarcinoma:
Barrett esophagus (metaplasia to intestinal-type columnar epithelium cells)
GERD
SCC:
tobacco
alcohol
achalasia (dysmotility)
discuss the 2 types of scleroderma
Scleroderma: triad of autoimmunity, vasculopathy, and collagen deposition
Diffuse scleroderma:
widespread skin involvement, rapid progression
anti-Scl-70 Ab
Limited scleroderma: limited skin involvement (fingertips and face) CREST syndrome Calcinosis (around veins) Raynaud phenomenon Esophageal dysmotility Sclerodactyly (thick skin) Telangiectasia Anti-centromere Antibody!
describe octreotide’s function in esophageal varices specifically as well as generally
synthetic analog of somatostatin
inhibits the release of vasodilator hormones, thus causing splanchnic vasoconstriction, which decreases portal flow, and decreases vatical bleeding
also treats acromegaly
also treats diarrhea in various endocrine disorders
describe what chief cells, D cells, G cells, parietal cells, S cells, and I cells secrete
chief cells:
in gastric body and antrum
secrete pepsinogen
D cells: gastric antrum and duodenum secrete somatostatin (inhibitory effects), which suppresses gastrin, insulin, CCK, pancreas secretions, and bile flow
G cells:
gastric antrum
secrete gastrin, which stimulates secretion of gastric acid by parietal cells and pepsinogen by chief cells
Parietal cells:
gastric mucosa
secrete HCl
S cells:
Small intestine
secrete secretin in response to low duodenal pH to protect SI mucosa from acid and increase bicarb secretion from pancreas and bile ducts
I cells:
duodenum and jejunum
secrete CCK in response to FAs and AAs
discuss Motilin and MMCs
MMCs are migrating motor complexes
they occur every 90-120 min between meals, beginning in stomach and going to ileum, then die out
general cleansing function, sweeping undigested food, debris, and bacteria through intestine to prep for next meal
eating disrupts MMC
in absence of MMCs, you’ll get bacterial overgrowth
Motilin produces the MMCs during fasting states
Motilin is only found in small intestine
HLA-DR5 is associated with
Hashimoto Thyroiditis
Which two HLA’s are associated with T1DM?
HLA-DR3 and HLA-DR4
Imagine: Type “1”, (not type 2, so skip 2), then 3 and 4
discuss IgA immunity
serum IgA = mucosal immunity
Which two vaccinations are Sabin and Salk for polio?
Sabin = live attenuated
IgA mucosal response
IgG response
this vaccine gives you potential to infect others via stool shedding, so it’s not used in US
Salk = inactivated/killed
IgG only; used in United States
describe a reasonable way to think through bleeds 2/2 vomiting/ucler
posterior duodenal wall = gastroduodenal artery; picture duodenum traveling directly in front of stomach
Lesser curve of stomach = R gastric artery (or L gastric off celiac)
Greater curve of stomach = L gastroepiploic artery (off of gastroduodenal)
duodenum to proximal 2/3 of transverse colon = SMA
describe why insulin levels are higher with oral vs IV glucose admin
GI gut hormones called Incretins stimulate pancreatic insulin secretion in response to sugar-containing meals
Incretin secretion is independent of blood glucose levels (happens before rise in blood glucose, too)
Incretin activates GLP-1 and GIP
IV glucose increases insulin 2/2 sensitivity of pancreatic beta cells’ response to blood glucose
discuss difference between essential fructosuria and fructose intolerance
fructose metabolism occurs in liver
essential fructosuria:
asymptomatic
defect in fructokinase
fructose can’t go to F1P, glycerol, or glycolysis, etc.
but fructose is not trapped inside cells because it can go back to glucose via Hexokinase
(you have a problem w/ fructose metabolism, but it’s “kind enough” not to interfere w/ your life)
fructose intolerance:
symptomatic
defect in aldolase B, which takes F1P–> DHAP or glyceraldehyde
you have hypoglycemia, jaundice and vomiting after fructose ingestion (fruit, juice, honey)
urine dipstick is neg (only looks at glucose)
tx: diet- don’t eat fructose OR sucrose (glu + fructose)
what’s the way to remember the glycogen storage disease orders
Very Poor Carb Metabolism
Type 1- Von Gierke
Type 2- Pompe
Type 3- Cori
Type 5- McArdle
all of them cause accumulation of glycogen inside of cells, therefore
PAS stain positive!
these are all auto recessive (there’s 12 total)
discuss Von Gierke disease
Type 1 glycogen storage disease
Defect in Glucose 6 Phosphatase, which normally converse G6P back to glucose
Impaired gluconeogenesis and glycogenolysis (cannot go “backwards” up in the last step of the pathway chart)
Presents: SEVERE fasting hypoglycemia very high glycogen in liver high blood lactate high triglycerides high uric acid (Gout) hepatomegaly
Tx:
frequent oral glucose
Avoid fructose and galactose
discuss Pompe disease
Type 2 glycogen storage disease
Defect in alpha-1,4-glucosidase
AKA acid maltase
takes place in lysosomes only
it’s supposed to remove the entire glucose-chain nub off the molec
Presents:
Cardiomegaly, hypotonic muscles in infant
“Pompe trashes the pumps” incl heart, liver, and muscles, leading to early death <2yo
pts do not have hypoglycemia problems
Treat:
give alpha-1,4-glucosidase
discuss Cori disease
Type 3 glycogen storage disease
Defect in debranching enzyme alpha-1,6-glucosidase
(the “b” in debraching looks like a 6 maybe?)
it takes the final glucose nub off the branched molecule- imagine the b bump being the last nub
Presents:
milder form of Von Gierke
gluconeogeneis is intact, but glycogenolysis isn’t
normal blood lactate levels
accumulation of “ limit dextrin like” structures in cytosol
discuss McArdle disease
Type 5 glycogen storage disease
defect in glycogen phosphorylase in skeletal muscles (myophosphorylase) which is supposed to take the big glucose chains off the molec
Presents:
high glycogen in muscles, but muscle cannot break it down
painful muscle cramps
myoglobinuria w/ exercise
arrhythmias from electrolyte abnormalities
“Second-wind” phenomenon due to increased muscular blood flow
blood glucose levels are typically unaffected
“Mcardle = Muscle”
discuss fatty acid synthesis vs fatty acid degradation
fatty acid synthesis: "Citrate = Synthesis" in well-fed state start with citrate in mitochondria use the citrate shuttle to go to cytoplasm then need ATP citrate lyase to turn into Acetyl-CoA then go to Malonyl-CoA then go to FA synthesis (palmitate)
fatty acid degradation:
“Carnitine = killing/carnage of fatty acids”
in a starved state:
start w/ Fatty acid + CoA in cytoplasm
use Fatty acid CoA synthase to go to Fatty acyl-CoA
then use carnitine shuttle to go to mito matrix
then undergo beta-oxidation w/ Acyl CoA dehydrogenase to make Acetyl CoA
Acetyl CoA can turn into ketone bodies or go to the TCA cycle
**Malonyl CoA inhibits the transfer of Fatty acid to the mito matrix via inhibiting carnitine acetyltransferase; therefore inhibiting FA degradation/beta oxidation
discuss 2 types of gallstones
high cholesterol or bilirubin, low bile salts, and gallbladder stasis all lead to stones
cholesterol stones:
most common
obesity, Crohn, age, estrogen therapy, multiparty, rapid weight loss, Native Americans
Pigment stones:
Ca + unconjugated bilirubin
black- Calcium bilirubinate, hemolysis
brown- infection; releasing beta-glucuronidase by injured hepatocytes and bacteria, which increases unconjugated Bilirubin
seen w/ Crohn, chronic hemolysis, alcoholic cirrhosis, age, biliary infections, TPN (bile stasis)
discuss pyruvate dehydrogenase deficiency
defect in a middle step in turning glucose into the TCA cycle
defect in Pyruvate Dehydrogenase
Pyruvate cannot go to Acetyl CoA, which is supposed to go to TCA cycle (transition point from glycolysis to TCA cycle)
build up of pyruvate, which gets shunted to lactate (via LDH) –> lactic acidosis and also shunted to alanine (via Alanine aminotransferase ALT)
Findings:
neuro defects, lactic acidosis, high serum alanine
starts in infancy
treatment:
ketogenic diet- high in Lysine and Leucine (“Lyle and Lucy” eat keto); they cannot be metabolized to pyruvate and will not lead to increased production of Lactic Acid
–low carb/glucose diet so you don’t have to do glycolysis
discuss LDH deficiency
defect in Lactate Dehydrogenase
LDH normally helps in converting pyruvate to Lactate in the Cori Cycle
it converts NADH to NAD+
when O₂ is depleted (exercising muscle), you use LDH for anaerobic glycolysis
if you have LDH deficiency, then you have low NAD+, which leads to fast muscle fatigue/breakdown
what is somatostatin’s function
decrease GH and TSH
used to treat gastronoma, acromegaly, carcinoid syndrome, glucagonoma, and esophageal varices
somatostatin comes from pancreatic delta cells
overproduction causes decrease in secretin, CCK, glucagon, insulin, and gastrin
discuss using the Aa gradient to determine the cause of a pt’s hypoxemia
4 major causes of hypoxemia, which is low PaO2 (low O₂ in arteries): alveolar hypoventilation V/Q mismatch diffusion impairment R-->L shunting
pAO2 is normally 104mmHg, and by the time it becomes systemic, it drops to 100 (bronchial circulation blood mixes), so an Aa gradient is normally between 5-15mmHg.
If a pt is hypoxemic with a normal Aa gradient, then you know the low PaO2 is directly due to the low pAO2; so it’s not due to V/Q mismatch or an O₂ diffusion impairment.
Hypoxemia with a nl Aa gradient can be caused by:
alveolar hypoventilation or high altitude
beta-myosin heavy chain mutation is associated with which disorder
Hypertrophic cardiomyopathy
this is a sarcomere protein defect
autosomal dominant
alpha fetoprotein is a useful serum tumor marker in what 2 tumors
HCC
germ cell tumors
CA 19-9 and CA 125 are useful serum tumor markers in what
CA 19-9 = pancreatic
CA 125 - ovarian
carcinoembryonic antigen (CEA) is a useful serum tumor marker in what
GI (colorectal)
hCG is a useful serum tumor marker in what 2 tumors
choriocarcinoma
germ cell tumors
describe the 3 types of pneumonias w/ its stages
patchy infiltrates = bronchopneumonia
alveolar walls w/ inflammatory infiltrate = interstitial
entire lobe = lobar
4 lobar stages:
congestion (first 24 hrs)
macro: affected lobe is red, heavy, and boggy
micro: vascular dilation; and alveolar exudate contains mostly bacteria
Red hepatization (2-3 days)
macro: red, firm lobe (“liver-like”)
micro: alveolar exudate contains erythrocytes, neutrophils, and fibrin
Gray hepatization (days 4-6)
macro: gray-brown firm lobe
micro: RBCs disintegrate; alveolar exudate contains neutrophils and fibrin
Resolution
Macro: restoration of nl architecture
micro: enzymatic digestion of exudate
how is work of breathing minimized w/ the two types of pulmonary diseases
obstructive:
WOB is minimized by breathing slow, deep breaths (lower rate and high TV)
Restrictive:
WOB is minimized by breathing fast, shallow breaths
(higher rate and low TV)
higher TVs increase the work needed to counteract the elastic resistance of the lung
discuss clinical picture of Cystic Fibrosis vs Kartagener’s Syndrome
Cystic Fibrosis:
recurrent pulm infections, chronic bronchitis/bronchiectasis –> reticulonodular CXR
pancreatic insufficiency w/ malabsorption, steatorrhea, and fat-soluble vitamin deficiency
Infertility in men (absent Vas Deferens; spermatogenesis may be normal), subfertility/thick cervical mucus in females
Nasal polyps, nail clubbing
Kartagener syndrome (primary ciliary dyskinesia):
immotile cilia 2/2 defective dynein
M/F infertility (immotile sperm and dysfunctional fallopian tube)
risk of ectopic pregnancy
bronchiectasis, recurrent sinusitis
situs inversus (dextrocardia CXR)
MEN classifications
MEN 1: PPP Parathyroid (hypercalcemia) Pituitary (PRL, visual) Pancreatic (esp gastrinoma)
MEN 2A: PPM Parathyroid Pheochromocytoma (adrenal) Medullary Thyroid Cx (Calcitonin)
MEN 2B: PMM Pheochromocytoma Medullary Thyroid Cx Mucosal neuromas/Marfanoid Habitus
discuss the changes of myocardial tissue after an MI
immediately: minimal/no change
up to 1 Day:
coagulative necrosis, edema, hemorrhage, wavy fibers, marginal contraction bands
up to 1 Week:
coag necrosis w/ neutrophil, then macrophage infiltrate
1 Month:
continued macrophage phagocytosis
granulation tissue w/ neovascularization
collagen deposition/scar formation
What does TNF-alpha do?
mediates paraneoplastic cachexia in humans via suppressing appetite (hypothalamus) and increasing basal metabolic rate
What histologically is seen with AML? how does it present? translation?
what can you treat it with?
Auer rods, which stain with myeloperoxidase
Pt will present with anemia, leukopenia, and thrombocytopenia symptoms as a result from the marrow being replaced by leukemic cells- often shows up as DIC
t(15:17) gives APL subtype, which is associated with PML/RARalpha fusion gene
the APL subtype responds to all-trans-retinoid acid ATRA- Vitamin A
What are KRAS mutations associated with
KRAS is a porto-oncogene that encodes a GTP-associated protein (GAP) associated with Epidermal Growth Factor Receptor EGFR, among others, which promotes increased cell proliferations and growth
Active Ras is bound to GTP and uses GAP to inactivate it with GDP.
Ras mutations cause it to be permanently activated, which activate the MAP kinase pathway and activate transcription.
KRAS mutations are found in different types of cancers, including a large portion of metastatic colon cancers
What is a Sudan III stain useful for
identifying unabsorbed fat and confirming malabsorption from a stool sample
useful in initial eval of a pt with signs of malabsorption
what are the cell markers for pre T and B cell lymphoblasts, respectively
pre-T lymphoblasts express CD2 CD3 CD4 CD5 CD7 CD8
pre-B lymphoblasts express
CD10
CD19
CD20
TdT is seen in both
how does ALL commonly present
common in children
T-cell ALL can present as a mediastinal mass, that causes mass-effect such as SVC syndrome or tracheal compression w/ dyspnea and stridor, or esophagus w/ dysphagia
B-cell ALL is more common but doesn’t present w/ mass effect- it presents w/ fever, malaise, bleeding, bone pain, HSM
what is required to be seen on histo to dx Hodgkin Lymphoma
Reed Sternberg Cells
seen on a background of lymphocytic infiltrates
Discuss nausea and vomiting
Area postrema in 4th ventricle is AKA chemoreceptor trigger zone for vomiting
The Nucleus Tractus Solitarius (NTS) is in the medulla. It receives info from the area postrema, GI tract via Vaugs nerve, vestibular sys, and CNS
5 major receptors contribute to the vomiting reflex:
M1 muscarinic (motorcycle in the parking lot)
D2 dopaminergic (2 D athlete ropes)
H1 histaminic (sailors swatting bees)
5-HT3 serotonergic (shot put balls)
Neurokinin 1 (NK1) (plaNK1 horse)
5-HT3 and NK1 receptor antagonists are particularly useful for chemotherapy-induced vomiting.
5-HT3 blocker is ondansetron (happy dancer in front of shot put)
NK1 blocker is Substance P and Aprepitant (urine test from participants)
describe pilocytic astrocycoma
most common childhood brain tumor, usually in cerebellum
GFAP positive
Rosenthal fibers (eosinophilic corkscrew fibers)
Imagine a child laying w/ his hair on a pillow looking up at stars and roses, and considering FAPping lolz
describe medulloblastoma
childhood brain tumor
located exclusively in cerebellum
highly malignant- “drop metastases” into cauda equina
primitive neuroectodermal tumor
can compress 4th ventricle–> noncommunicating hydrocephalus
see many small blue cells that form Homer Wright rosettes (groups of cells surrounding the neuropil)
imagine Adam Sandler in the Waterboy w/ “medulla” scene- he’s not communicating well, while the teacher has the big head (hydrocephalus). He knows his momma at Home is Wright, and he drops off 4 rosettes on his horse
describe ependymoma
childhood brain tumor
ependymal tumors most commonly found in 4th ventricle
can cause hydrocephalus
characteristic perivascular rosettes
rod-shaped blepharoplasty (basal ciliary bodies) found near nucleus
Imagine 4 roses, but someone has drawn on vasculature w/ a pen
describe carniopharyngioma
childhood brain tumor
may be confused with pituitary adenoma (both cause bitemporal hemianopsia)
derived from remnants of Rathke pouch- anterior pituitary
Calcification is common
cholesterol crystals found in “motor-oil” like fluid within tumor- “wet keratin”
Imagine a pharyngioma Pharaoh forcing you to experience his Rathke by pushing you into a PIT of bones (calcium) and eat carrots dipped in motor oil and cholesterol
describe pinealoma
childhood brain tumor
pineal gland tumor
can cause Parinaud syndrome (compression of tectum –> vertical gauze palsy)
obstructive hydrocephalus
precocious puberty in M (beta-hCG production)
histologically similar to germ cell tumors
Imagine looking up (vertical gaze) and being paranoid (Parinaud syndrome) of God (vertical) getting the big head (hydrocephalus) and obstructing (obstructive) all pine trees (pineal)
describe glioblastoma multiforme
AKA grade IV astrocytoma
common, highly malignant
in cerebral hemispheres; crossing corpus callosum = butterfly glioma
“pseudopalisading” pleomorphic tumor cells - border central areas of necrosis and hemorrhage
GFAP positive stain
Imagine butterflies gliding (glio) across all hemispheres of the earth, almost as if they’re para-sailing (pseudo-palisading), but they’re actually FlAPping their wings. They border the palace areas w/ necrosis and hemorrhage
describe Meningioma
common, typically benign brain tumor
most often near surfaces/falcine and parasagittal regions
arise from arachnoid cells, extra-axial, and may have dural attachment (tail)
often asymptomatic, but may get HA worsening w/ sleep
see spindle cells in a whorled pattern and psammoma bodies
Imagine dreaming (sleep) that an MAN (meningioma) arachnoid spider w/ a tail (dural attachment) on your bathroom shower porcelain surface (falcine/parasagittal surface). He can go unnoticed (asymptomatic), but momma (psammoma) decides to turn the water on and watch him whirl(whorled spindle cells) around the drain anyway
describe Hemangioblastoma
associated with von Hippel-Lindau syndrome when found w/ retinal angiomas.
can produce EPO, leading to secondary polycythemia
close, thin-walled capillaries w/ minimal intervening parenchyma
imagine an erythro- Hippo who’s got bloodshot eyes staring at a He-Man named Lin
Describe Schwannoma
classically at cerebellopontine angle, but can be along peripheral nerves
often localized to CN 8–> vestibular schwannoma. Bilateral vestibular schwannomas associated with NF-2
Schwann cell origin, S-100 positive
presents w/ hearing loss/tinnitus, loss of balance
histo: spindle cells w/ palisading nuclei arranged around Verocay bodies (eosinophilic cores)
imagine 100 deaf swans wearing “velcro” vests who fall into BOTH SIDES (bilateral, NF-2) of the pink pond edge (eosinophils, cerebellopontine angle) because they lost their balance parasailing around
Describe oligodendroglioma
most often in frontal lobes, rare, slow growing
“chicken wire” capillary pattern
oligodendrocytes = fried eggs- round cells w/ clear cytoplasm
often calcified
Rarely, we-all-go get breakfast w/ chicken, fried eggs, and white calci-Yum milk
Describe Pituitary adenoma
most commonly a prolactinoma, or nonfunctioning
bitemporal hemianopsia from optic chiasm compression
could also be lactotroph, gonadotroph, somatotroph, or corticotroph
describe M hormone gonadal axis
pulsatile GNRH in hypothalamus goes to
pituitary gland
pituitary gland releases FSH and LH
LH stimulates release of testosterone form Leydig cells of testis
FSH stimulates the release of Inhibin B from Sertoli cells
Testosterone has a neg feedback effect on LH and GnRH
Inhibin B has a neg feedback effect on FSH
FSH levels may be higher in M w/ only 1 testicle since they have fewer sertoli cells producing the inhibitory Inhibin B
discuss pathophysiology of functional hypothalamic amenorrhea
commonly found in young F with pressure to be thin
may be seen w/ F who used to have nl menses but they’re now irregular/absent
due to decreased circulating leptin levels 2/2 diminished adipose tissue stores.
decreased leptin inhibits pulsatile GnRH lease, which decreases LH and FSH secretion, circulating estrogen, and amenorrhea
describe familial hypercholesterolemia
auto dominant
LDL receptor malfunction leading to accelerated atherosclerosis and early-onset CAD
70% of plasma LDL is normally cleared by the liver’s LDL receptors
describe the 4 subtypes of thyroid cancer
Papillary carcinoma:
most common; ionizing radiation (acne tx) is common risk factor
papillae w/ “orphan annie eye” cells and nuclear grooves (coffee beans), and psammoma bodies
Annie cells described as “large cells with finely dispersed chromatin and ground-glass appearance)
Imagine “orphan annie” doesn’t have a pappi or a psammoma
Follicular carcinoma:
follicle surrounded by a capsule WITH invasion
“hope your cap doesn’t break if you fall”
Medullary carcinoma:
associated with MEN2 and RET gene
parafollicular C cells (neuroendocrine cells that secrete calcitonin)
calcitonin may deposit as amyloid, which stains apple green with Congo Red
“Amy tries to “C” a pair of 2 Men at the Congo, but Ed, Lary and Cal say “no no”
Anaplastic carcinoma:
undifferentiated malignant cells in elderly
large pleomorphic giant cells
invades local structures producing dysphagia or resp compromise (similar to Riedel Fibrosing Thyroiditis in young pt)
describe glucagonoma
tumor of pancreatic alpha cells, causing overproduction of glucagon
presents w/ hyperglycemia (often as newly diagnosed diabetes mellitus) and necrolytic migratory erythema (blistering erythematous plaques w/ central clearing around groin, face, extremities, may transform to bronze/brown central indurated area w/ peripheral blistering and scaling)
Presents w/ 5 D's: Dermatitis Diabetes DVT Declining weight Depression
differentiate between DIC and TTP-HUS
DIC: patients bleed coag cascade is activated PT and PTT are prolonged low fibrinogen and increased FDP (fibrin degradation products, esp D-dimer)
TTP-HUS: usually do not bleed only plts are activated normal PT/PTT normal Fibrinogen
differentiate between vWF deficiency and Hemophilia A
vWF:
normal or prolonged PTT
prolonged bleeding
pts often present w/ lifelong hx of mucosal bleeding
nl platelet levels but prolonged bleeding due to impaired plt functioning
Hemophilia A:
high PTT, but normal bleeding time
characteristic deep-tissue bleeding (into joints, GI bleeds, hematuria)
differentiate between esophageal cancer risk factors and histology of squamous cell and adenocarcinoma
Squamous cell carcinoma:
alcohol and tobacco
consumption of N-nitroso-containing foods (smoked Japanese); also hot liquids
Histology shows ovoid epithelial cells w/ eosinophilic cytoplasm, keratin pearls, and intercellular bridging; commonly with large hyerpchromatic cells w/ bizarre nuclei and atypical mitoses
Adenocarcinoma: Barrett's esophagus GERD Obesity Tobacco Adenocarcinoma is more common in America, so correlate that to Barrett's/GERD
what are the 2 substances that mediate angiogenesis in neoplastic and granulation tissue
VEGF
FGF
what is intravascular hemolytic anemia characterized by?
decreased serum haptoglobin (bind free Hb; decrease when large quantities of Hb are released into circulation)
increased LDH
increased bilirubin
describe hairy cell leukemia
it’s an indolent B cell neoplasm
bone marrow infiltration causes fibrosis, bone marrow failure, and pancytopenia, so you get a “dry tap”
massive splenomegaly (crossing midline) from spleen red pulp infiltration
histo shows lymphocytes w/ cytoplasmic projections
describe Burkitt Lymphoma’s genetic problem
t(8;14)
affects c-myc gene
large jaw mass
histo shows starry sky pattern
what is BCR-ABL associated with
CML
the mutation increases tyrosine kinase activity
what is BCL2 overexppresion associated with
follicular lymphoma
t(14;18) translocation
generalized LAD
normally, BCL2 inhibits apoptosis
n-myc is associated with
neuroblastoma
describe Hep A histology
spotty necrosis with ballooning degeneration (hepatocyte swelling w/ wispy/clear cytoplasm), councilman bodies (eosinophilic apoptotic hepatocytes), and mononuclear cell infiltrates
pts present acutely w/ fever, malaise, anorexia, N/V, RUQ pain
several days later have cholestasis, jaundice, pruritus, dark-colored urine (increased conjugated bilirubin levels), and echoic stool (lacks bilirubin pigment)
self-limited, doesn’t progress to HCC
describe Kallmann syndrome
absence of GnRH neurons in hypothalamus 2/2 defective migration from olfactory placode
pts have central hypogonadism and anosmia; may have other midline defects (cleft lip)
often present w/ delayed puberty
some public hair because adrenarche occurs normally
describe hemolytic disease of the newborn for Rh and ABO scenarios
Rh:
Rh(-) mom has an Rh(+) baby, some fetal blood enters maternal circulation (delivery), and mom creates anti-D IgG against Rh antigen.
Rh(-) mom has an Rh(+) baby again, but this time has the IgG plasma antibodies, which crosses placenta and causes erythroblastosis fetalis.
To prevent this, give the mother anit-D IgG (RhoGAM) during third trimester, which prevents maternal anti-D IgG production. Babies will have positive direct Coombs test (indicating autoimmune hemolysis), anemia, jaundice, and edema/hydrops fetalis, immature/nucleated RBCs, and extra medullary hematopoiesis (HSM).
ABO:
type O mother has an A,B, or AB fetus. She’s had IgG (the non-pregnancy ex has IgM written?) antibodies against these her entire life.
name the types of hemoglobin
Hb Barts = gamma tetramers (in utero)
no alpha globin chains; causes hydrops fetalis
HbF = alpha2gamma2
HbA = alpha2beta2
HbA2= alpha2delta2
HbC= alpha2betaLysine2 (mutated beta chain- “C has lysine”)
HbS= alpha2betaS2 (mutated beta)
what is a positive Ristocetin test indicative of?
vWF disease
vWF normally binds GP1b on plts to allow for plt adherence, then aggregation. vWF also carriers Factor 8 and prolongs its half life.
vWF deficiency impairs plt function (with nl plt numbers) and presents as easy bruising and mucocutaneous bleeding (gingival, menses). A functional deficiency of Factor 8 also leads to prolonged bleeding after minor procedures.
Ristopetin activates platelet GP1b receptors and makes them available for vWF binding. but if vWF levels are decreased, there’s poor plt aggregation in the presence of ristocetin.
whats the substitution in Sickle Cell
glutamic acid –> Valine
ex. GAG –> GTG
describe primary hemochromatosis
mutation in HFE protein. HFE normally interacts w/ transferring receptor to form a complex that senses the status of iron stores.
Inactivating HFE mutations causes RBCs and hepatocytes to detect falsely low iron levels, so iron accumulation is increased 2 ways:
Enterocytes increase transport/absorption from GI lumen
Hepatocytes decrease hepcidin synthesis, allowing for increased iron secretion in circulation and causing Fe overload
Fe overload gives you triad:
micro nodular cirrhosis
diabetes mellitus
skin pigmentation- “bronze diabetes”
increased risk for HCC, CHF, and testicular atrophy
what is the cell surface marker of macrophages
CD14
think TB
also CD40, CCR5, MHC class 2, B7 (CD80/86), Fc and C3b receptors (enhanced phagocytosis)
what are the cell surface makers for NK cells
CD16 (binds Fc of IgG)
CD56 (unique for NK)
don’t require thymus to be made
member of innate immunity
induced to kill when exposed to nonspecific activation signals on target cells, or if there’s an absence of MHC class 1 on target cell surface
also kills via antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of Ig, which activates NK cell)
what’s the surface marker for hematopoietic stem cells
CD34
these cells can go on the myeloid path, or the lymphoid path
what are the regulatory T cell surface markers
CD4, CD25
what are the cytotoxic T cell surface markers
CD8
CXCR4/CCR5 (co-receptors for HIV)
what are the helper T cell surface markers
CD4, CD40L
what are the generic T cell surface markers
TCR (binds antigen-MHC complex)
CD3 (associated with TCR for signal transduction)
CD28 (binds B7 on APC)
CXCR4/CCR5 (co-receptors for HIV)
HLA subtypes for diseases: A3 B8 B27 DQ2/DQ8 DR2 DR3 DR4 DR5
A3 = hemochromatosis
B8 = Addison disease, Myasthenia Gravis
B27 = “PAIR” Psoriatic arthritis, Ankylosing spondylitis, IBD-associated arthritis, Reactive arthritis/Reiter
AKA seronegative arthropathies
DQ2/DQ8 = Celiac disease
“I ate too much gluten at Dairy Queen”
DR2 = MS, SLE, Goodpasture
DR3 = DM1, SLE, Graves, Hashimoto, Addison
DR4 = Rheumatoid arthritis, DM1, Addison
“4 walls to a room”
DR5 = Pernicious anemia –> Vit B12 deficiency, Hashimoto
describe major functions of B and T cells
B cells:
recognize antigen, and undergo mutation to optimize antigen specificity
produce antibody, and differentiate into plasma cells to secrete specific Immunoglobulins
Maintain immunologic memory, and memory B cells persist and accelerate further response to antigen
T cells:
CD4+ T cells help B cells make Ab’s and produce cytokines to recruit phagocytes and activate other leukocytes
CD8+ T cells directly kill virus-infected cells
participate in delayed cell-mediated hypersensitivity (Type 4)
Participate in acute and chronic organ rejections
what’s the helpful way to remember cytokines
Hot T-bone stEAK
IL-1: fever (hot) IL-2: stimulates T cells IL-3: stimulates Bone marrow IL-4: stimulates IgE production IL-5: stimulates IgA production and eosinophils IL-6: stimulates acute-phase reactants
what type of cell is MHC class I expressed on
all nucleated cells (not mature RBCs)
which cytokines are secreted by macrophages, and what are their functions
IL-1:
causes fever and acute inflammation
induces chemokine secretion to recruit WBCs
IL-6:
production of acute-phase proteins
IL-8:
major chemotactic factor for neutrophils- PUS
“clean up on aisle 8”- neutrophils recruited by IL-8 to clear infections
IL-12:
differentiation of T cells into Th1 cells
activates NK cells
TNF-alpha:
mediates septic shock, WBC recruitment, vascular leak, causing fever, hypotension, leukocytosis, and tachycardia
causes cachexia in malignancy!
what cytokines are secreted by T cells, and what’s their fucnction
all T cells: IL-2 and IL-3
Th1 cells: Interferon-gamma
TH2 cells: IL-4, IL-5, IL-10
IL-2:
stimulates T cells:
stimulates growth of helper, cytotoxic, and regulatory T cells; and NK cells
IL-3:
stimulates BONE marrow
supports growth/differentiation of bone marrow stem cells
Interferon-gamma:
from Th1 cells and NK cells
secreted in response to IL-12 from macrophages; stimulates macrophages to kill phagocytosed pathogens; inhibits differentiation of Th2 cells; activates NK cells to kill virus-infected cells
IL-4: from Th2 cells induces differentiation of T --> Th2 cells promotes growth of B cells enhances class switching to IgE and IgG
IL-5:
from Th2 cells
promotes growth/differentiation of B cells
enhances class switching to IgA
stimulates growth/differentiation of eosinophils
IL-10:
from Th2 cells and Treg cells
attenuates inflammatory response
decreases expression, inhibits activation
“TGF-beta and IL-10 both atTENuate the immune response”— WOUND HEALING
what do Interferon alpha and beta do
part of innate host defense against viruses
they are glycoproteins that are synthesized by virus-infected cells that act locally on uninfected cells, “priming them” for viral defense by helping to selectively degrade viral nucleic acid and protein
“interfere w/ viruses’
what is the bleeding disorder associated with hemarthrosis and how is it acutely treated?
Hemophilia
you could give Factor 8 or 9, depending on if it’s A or B/Christmas, or you could give Thrombin
Activated Factor 10a goes to 5a, which turns prothrombin into thrombin (Factor 2a), which turns fibrinogen into fibrin (Factor 1a)
then Factor 13a is used to make a cross-linked fibrin clot
remember thrombeaver has 2 front teeth
and fibrin/fibers are usually very thin/stick-like, so they’re represented as a 1
describe the process of T cell maturation
T cells arrive in sub capsular zone of thymus:
CD4 neg and CD8 neg
“double negative”
T cells migrate to the cortex, where they gain CD4 and CD8 markers
“double positive”
there’s positive selection where only T cells expressing a TCR that is capable of binding self MHC are allowed to survive. otherwise, they’re eliminated
T cells migrate to the medulla, where they interact w/ medullary and dendritic cells and become “single positive” of either CD4+ or CD8+
negative selection occurs by eliminating cells when there’s excessive affinity for self-antigens or MHC. this serves to eliminate T cells that may be overly reactive against self-antigens and may contribute to autoimmunity if not destroyed.
the CD4+ cells go on to become helper T cells
the CD8+ cells go on to become cytotoxic T cells
which leukemia is associated with Down Syndrome
ALL
not PC at all, but remember that Coach W had ALL……
what is Chronic Myelogenous Leukemia associated with
Philadelphia chromosome, t(9:22)
this fuses the BCR-ABL genes
culture difference between yeast, hyphae, and pseudohyphae
yeast = circles
hyphae = smooth branches
pseudohyphae = branches w/ notches
blebs at the end = candida
describe how a sideroblastic anemia might develop
defect in heme synthesis 2/2 X-linked defect in delta-ALA synthase gene
can be genetic, acquired, or reversible (alcohol, lead, Vit B6 deficiency, Cu deficiency, INH meds)
Heme is made of Fe and protoporphyrin
to make Protoporphyrin, Succinyl CoA +ALAS + VitB6 --> ALA (+ALAD) --> porphyobilinogen --> protoporphyrin
then, in the mitochondria, protoporphyrin + Fe via ferrochelatase to make Heme
if this process is disrupted, Fe is trapped in the mitochondria, Heme isn’t made, and you get ringed sideroblasts
describe G6PD deficiency and Pyruvate kinase deficiency
both result in an intrinsic, hemolytic, normocytic anemia (high Reticulocytes)
G6PD deficiency:
G6PD provides NADPH needed to reduce Glutathione in order to let it continue to neutralize H2O2 via oxidation
G6PD deficiency means you’re susceptible to oxidative stress; severity depends on how severe the half life of G6PD is decreased (African = mild; Mediterranean = severe)
the oxidative stress puts Hb as Heinz bodies, which are removed in spleen to make bite cells
Pyruvate kinase deficiency:
has elevated indirect bilirubin
you have low ATP, giving you rigid RBCs, causing extravascular hemolysis from spleen (splenomegaly), causing echinocyte “burr cell” w/ small uniform projections
Describe antibody structure
Fab (Fragment, antigen binding) consists of light and heavy chains that recognize antigens. it’s the top 2 branches of the Y
Heavy chain is the majority of the Y, and the light chain is the 2 extra lines off the top of the Y
The Fc region is the trunk of the Y (so Heavy chain contributes to Fc and Fab regions. Light chain only contributes to Fab.)
Fc is constant, carboxyl terminal, complement binding, carb side chains, and determines isotope (IgM, IgD, etc)
describe the different immunoglobulin isotypes
mature, naive B cells express IgM and IgD prior to activation (you get to “be” an “MD” once you’re mature, even if you’re naive)
B cells may differentiate into plasma cells by isotope switching. the plasma cells secrete IgA, IgG, or IgE (you differentiate as you AGE)
IgG:
main Ab in delayed response to antigen
most abundant
crosses placenta
IgA:
prevents attachment to mucus membranes in GI tract
most produced, but lower serum concentrations
released into secretions (tears, mucus, breast milk)
picks up the secretory component from epithelial cells which protects the Fc portion from luminal proteases
IgM:
produced in the primary/immediate response to antigen
does not cross placenta
its pentamer form allow avid antigen binding while the humoral response evolves
IgD:
unclear function. surface of many B cells
IgE:
binds mast cells and basophils
cross-links when exposed to allergen (asthma)
mediates immediate hypersensitivity (type 1) via release of inflammatory mediators, such as histamine
mediates worm immunity by activating eosinophils
lowest concentration ins serum
“IgG is relevant during Gestation”
“IgA sees things you Ate”
“IgM is an iMMediate responder”
“IgE is allerg-E responsive and activates Eosinophils”
what changes as the oxygen-hemoglobin dissociation curve shifts right and left?
Right shift: ACE BATs right handed, and "unloads" (O₂) on the ball: Acid (high H+, low pH) CO₂ Exercise 2,3-BPG Altitude Temp there's decreased affinity of Hb for O₂ (facilitates unloading into tissue)
L shift: a decrease in the above factors (low H+, high pH) facilitates O₂ loading in the lungs (decreased unloading)
Left = Lower
peripheral tissues have higher concentrations of CO₂ and H+, which facilitate O₂ unloading from Hb (Bohr effect)
lung tissue O₂ binding to Hb releases H+ and CO₂ into a low-concentration environment (Haldane effect)
describe pathogenesis of Factor 5 Leiden
production of a mutant Factor V making it resistant to degradation by protein C, causing a hyper coagulable state.
Complications incl DVT, cerebral vein thrombosis, recurrent pregnancy losses
how does mRNA make different sequences
via alternative splicing-
where exons of the gene are reconnected in multiple ways during post-transcriptional processing
results in different mRNA sequences which gives you different proteins
distinguish acute intermittent porphyria from porphyria cutanea trada and lead poisoning
AIP:
defective PBG deaminase (porphobilinogen deaminase)
you get build up of PBG and D-ALA in urine
symptoms are the 5 P’s:
Painful abdomen
Port wine-colored urine
Polyneuropathy
PSYCH DISTURBANCES (EARLY)
Precipitated by drugs/alcohol, starvation
Treatment: glucose and heme to inhibit ALASynthase
Porphyria cutanea tarda:
defect in uroporphyrinogen decarboxylase
results in uroporphyrin in urine (tea-colored)
Presents LATE WITH bolstering photosensitivity
Lead poisoning:
early disorder = neuropsych (defect in D-ALAD)
late disorder = photosensitivity (defect in ferrochelatase)
differentiate between Idiopathic Aplastic Anemia, Parvovirus B19, and Myelodysplastic syndrome
Aplastic anemia:
progressive signs/symptoms of pancytopenia
thrombocytopenia- bleeding
anemia- pallor/fatigue
leuko/neutropenia- infections
absent splenomegaly, since there’s lack of available hematopoietic progenitor cells/ no extra medullary hematopoiesis
bone marrow bx is hypo cellular
Parvovirus B19:
aplastic crisis, but red cell aplasia only (pancytopenia in immunocompromised pts)
bone marrow bx is hypo cellular
Myelodysplastic Syndrome:
defect in stem cell maturation, leading to pancytopenia
Bone marrow bx is hyper cellular with misshapen cells/nuclei
describe Kaposi’s sarcoma
associated with HHV-8 and HIV
endothelial malignancy most commonly of skin, but also mouth, GI, and resp tract.
frequently mistaken for bacillary angiomatosis, but has lymphocytic infiltrate
blue-violet or brownish skin plaques
what are the mRNA processing steps that occur in the nucleus following transcription
5’ capping via addition of 7-methylguanosine cape
poly A tail addition via polyadenylation of 3’ end
intron splicing out
polyadenylation signal = AAUAAA
poly-A polymerase does not require a template
cytoplasmic P bodies play a role in mRNA translation regulation and degradation in the cytoplasm–
mRNA’s quality control
JAK-STAT pathway is used for what 3 things
Growth hormone binding surface receptors
cytokines (interferon)
hematopoietic growth factors (EPO, G-CSF)
what are the anion-gap metabolic acidosis causes
MUDPILES
methanol (formic acid) uremia DKA Propylene glycol Iron tablets or INH Lactic acidosis Ethylene glycol (antifreeze) Salicylates (aspirin)
use Winter’s formulas to check the compensation for a simple metabolic acidosis
describe use of Winters formula in a pt work-up
Predicted respiratory compensation for a simple metabolic acisosi can be calculated using the Winters formula.
measured CO₂ = lab value
predicted CO₂ = calculated CO₂
calculated pCO2 = 1.5 [HCO3-] + 8 +/- 2
lab > calc = superimposed resp acidosis
lab < calc = superimposed resp alkalosis (appropriate compensatory response)
a superimposed respiratory acidosis means your CO₂ is still high; you haven’t blown off enough; respiratory failure should be considered
what are the normal anion gap metabolic alkalosis disorders
HARDASS
Hyperalimentation Addison's Renal tubular acidosis Diarrhea Acetazolamide Spironolactone Saline infusion
what are the respiratory alkalosis disorders
Hyperventilation is the cause
hysteria hypoxemia (high altitude) salicylates (early) tumor pulm embolism
what are the respiratory acidosis disorders
hypoventilation is the cause
airway obstruction acute lung disease chronic lund disease opioids, sedatives weakening of resp muscles
what are the causes of metabolic alkalosis
loop diuretics
vomiting (lose HCl)
antacids hyperaldosteronism
loop diuretics respond to saline; hypoaldosteronisim is not saline responsive
CLEVER PD contraction (dehydration) licorice/laxative Endocrine (Conn's) Vomiting/GI loss Excess alkali (antacids) Renal (Bartter's), severe hypokalemia Posthypercapnia Diuretics
which 3 steps require a Thiamine cofactor
Thiamine is Vit B1
think ATP:
alpha-ketoglutarate dehydrogenase (TCA cycle)
Transketolase (HMP shunt)
Pyruvate dehydrogenase (links glycolysis to
TCA cycle)
Branched-chain ketoacid dehydrogenase (maple syrup urine disease)
how does Niacin deficiency present
3 D’s of B3: Pellagra
Dermatitis (sun-exposed areas- broad collar rash)
Dementia
Diarrhea
Hartnup disease:
auto receive disease of neutral AA (tryptophan) transporters in renal tubules and RBCs; leads to low tryptophan for conversation into Niacin
treat with high protein diet and nicotinic acid
describe glucokinase’s function and its mutation
insulin release by pancreatic beta cells is stimulated by increased ATP production
Glukokinase functions as a glucose sensor in pancreatic beta cells by controlling the rate of glucose entry into the glycolytic pathway
mutations in glucokinase cause maturity onset diabetes of the young (worsens during pregnancy)
describe cavernous hemangioma
benign liver and brain tumor
“bloody sponge” or “mulberry cluster” of vasculature appearance w/ dilated vessels separated by thin CT septa
biopsy is contraindicated due to risk of hemorrhage
in the brain, it could cause focal/neuro deficits
describe carpal tunnel syndrome
entrapped median nerve, causing decreased sensation of first 3 fingers and thenar atrophy (but not loss of sensation there)
median nerve courses between humeral and ulnar heads of pronator teres
then between flexor digitorum superficialis and flexor digitorum profundus
you could relieve symptoms by cutting the transverse carpal ligament (AKA flexor retinaculum) in the carpal tunnel
associated with dialysis-related amyloidosis, pregnancy, Rheumatoid arthritis, hypothyroidism, DM
describe Guyon canal syndrome
compression of ulnar nerve at wrist, classically in a cyclist 2/2 handlebar pressure
describe hemiballismus
movement disorder
sudden, wild flailing of 1 arm +/- ipsilateral leg
caused by damage to contralateral sub thalamic nucleus (part of basal ganglia), which normally plays a role in inhibition of the thalamus
most commonly due to lacunar stroke (2/2 longstanding HTN and DM)
damage to caudate nucleus causes what
Huntington
caudate nucleus is part of Basal ganglia
atrophy of lentiform nucleus causes what
Wilson disease
specifically the putamen, because the lentiform nucleus made of putamen and globus pallidus
degeneration of the substantia nigra causes what
Parkinson
what are the relevant clinical reflexes
S1,2- buckle my shoe
L3,4- kick the door
C5,6- pick up sticks
C7,8- lay them straight
L1,2- testicles move (cremaster reflex)
S3,4- winks galore (anal wink reflex)
describe locked in syndrome
pt is locked in their own body, often quadriplegic except for their eyes
caused by rapid correction of hyponatremia
rapid correction of hypernatremia will cause cerebral edema/herniation- commonly of Basilar artery
“low to high, the pons will die”
“high to low, your brain will blow”
which CNs control eye movements and how does damage present
LR6(SO4)3
CN 6- lateral rectus (abduct eye)
-Abducens
Damage presents as a medially directed eye that cannot abduct
CN 4- Superior oblique (up and in)
-trochlear
Damage presents as upward eye movement, esp w/ contralateral gaze; pt will often oil head toward the side of the lesion (compensatory head tilt in opposite direction)
pts will have trouble going down stairs and may complain of vertical diplopia
CN3- the rest
-oculomotor
Damage presents as ptosis, “down and out” gaze if the motor output is damaged; diminished/absent pupillary light reflex, blown pupil if the parasympathetic output is damaged.
-Commonly seen in vascular diseases, incl DM and sorbitol accumulation
Describe cranial nerve nuclei locations
located in tegmentum portion of brainstem (Between ventral and dorsal)
Lateral nuclei = aLar plate (sensory)
–sulcus limitans –
Medial nuclei = Motor (basal plate)
Nuclei: 4 above Pons 4 in Pons 4 below Pons CN 1,2 Midbrain- CN 3,4 Pons- CN 5,6,7,8 Medulla- CN 9,10,12 Spinal cord- CN 11
describe cranial nerve and vessel pathways
imagine the red, yellow, and blue diagram on p. 478
Anterior cranial fossa: has cribriform plate, and CN1
Middle cranial fossa (through sphenoid bovine), has
optic canal (CN2)
Superior orbital fissure (CN 3,4,5-1, 6)
foramen Rotundum (5-2)
foramen Ovale (5-3)
foramen spinosum- Middle meningeal artery
Posterior cranial fossa (through temporal or occipital bone) has Internal auditory meatus (CN 7,8) Jugular foramen (CN 9,10,11) Hypoglossal canal (CN 12) Foramen magnum (brainstem)
Remember for CN5: SRO
Remember “9, 10, 11 = jugular foramen”
describe PICA stroke
AKA lateral medullary syndrome AKA Wallenberg syndrome
posterior inferior cerebellar artery (PICA) occlusion; can occur w/ cervical spine trauma w/ dissection of vertebral artery
causes vomiting, vertigo, nystagmus, decreased pain/temp sensation from ipsilateral face and contralateral body; dysphagia, horseless, ipsilateral Horner syndrome, ataxia, dysmetria
“don’t PICA stag horn (nystagmus, horner’s) horse (hoarseness) that can’t eat (dysphagia) or follow a wall (ipsilateral; Wallenberg)”
describe MCA stroke vs ACA stroke
middle cerebral artery stroke:
contralateral paralysis and sensory loss- face and upper limb
can cause Wernicke’s aphasia if in temporal lobe
can cause Broca’s aphasia if in frontal lobe
Aphasia if in dominant (~left) hemisphere
Hemineglect if in non-dominant (~right) hemisphere
also causes “pie” vision problems
Anterior cerebral artery stroke:
contralateral paralysis and sensory loss- LOWER limb
describe a lenticulostriate artery stroke
a common location of lacunar infarcts 2/2 unmanaged HTN
the hypertensive vasculopathy involves the penetrating branches of the major cerebral arteries. the most frequently affected location is basal ganglia (putamen). the basal ganglia are supplied by lenticulostriate arteries, which are small branches off the MCA
small lake-like infarcts in striatum that accumulate and create one significant hemorrhage
describe anterior spinal artery stroke
ipsilateral tongue dysfunction (tongue deviates ipsilaterally)
describe posterior cerebral artery stroke
contralateral hemianopia with macular sparing!
what cells stain for synaptophysin? GFAP?
synaptophysin = neurons
GFAP = glial origin
astrocytomas, ependymomas, oligodendrogliomas
describe the ventral posterior nuclei (lateral and medial) and the geniculate nuclei (lateral and medial)
thalamic nuclei
VPL:
receives input from spinothalamic tract and dorsal columns
(drawn in your diagrams)
-pain, temp, pressure, tough, vibration, proprioception
VPM:
receives input from trigeminal pathway
(Makeup goes on the face)
-face sensation
they both send somatosensory projections to the cortex via thalamocortical fibers
damage to both results in complete contralateral sensory loss
Lateral geniculate nucleus: receives “L”ight input from CN2
Medial geniculate nucleus:
receives “M”usic input from superior olive and inferior colliculus of tectum
describe the symptoms of altered activity of the dopaminergic pathways:
mesocortical, mesolimbic, nigrostriatal, and tuberoinfundibular
mesocortical:
decreased activity = negative symptoms
(antipsychotic drugs have limited effect)
mesolimbic:
increased activity = positive symptoms
primary therapeutic target of antipsychotic drugs (to decrease the positive symptoms)
Nigrostriatal:
major dopaminergic pathway in brain
decreased activity = extrapyramidal symptoms
(controls coordination and voluntary movement; significantly affected by movement disorders and drugs)
tuberoinfundibulnar:
decreased activity = increased prolactin and associated effects
describe internuclear ophthalmoplegia
INO: commonly seen in MS
damage to MLF in dorsal pons
caused by reduced saltatory conduction with relative preservation of axons
eye on ipsilateral side of lesion has trouble adducting when looking in the opposite direction
(if the lesion is on the left and you try to look right- the left eye cannot look towards your nose)
convergence and pupillary light reflex are preserved
name wrist bones
Some Lovers Try Positions That They Can’t Handle
Scaphoid Lunate Triquetrum Pisiform --> Trapezium Trapezoid Capitate Hamate
start closest to thumb on both lines
what 3 injuries can happen in wrists
Scaphoid-
most commonly fractured (from a FOOSH)
prone to avascular necrosis (retrograde radial artery blood supply)
Lunate dislocation-
may cause carpal tunnel syndrome
Hook of hamate-
from FOOSH
can damage ulnar nerve
how does an axillary nerve injury present
an upper humerus injury:
fractured surgical head of humerus or anterior dislocation of humerus
presents w/
flat deltoid
loss of abduction at shoulder
loss of sensation over deltoid and lateral arm
how does musculocuatneous nerve injury present
upper trunk compression
presents:
loss of elbow flexion
loss of sensation over lateral forearm
how does radial nerve injury present
mid shaft humerus fracture, passing through supinator canal, compression of axilla (crutches), or sleeping over chair (saturday night palsy)
presents:
wrist drop (loss of extension)
decreased grip strength
loss of sensation over posterior arm, forearm, and dorsal hand
how does median nerve injury present?
recurrent branch of median nerve?
supracondylar fracture of humerus (proximal lesion)
carpal tunnel syndrome
wrist laceration (distal lesion)
presents:
ape hand
pope’s blessing
loss of wrist flexion
loss of sensation over thenar eminence and parts of lateral 3.5 fingers
Tinel sign (tingling on percussion) = carpal tunnel
recurrent branch: superficial palm laceration -presents: ape hand loss of thenar muscles but no loss of sensation
how does ulnar nerve injury present
fracture of funny bone of humerus (medial epicondyle) or fracture of hook of hamate
presents:
ulnar claw on digit extension
radial deviation of wrist
loss of wrist flexion, adduction, flexion of 4th/5th digits
loss of sensation over medial 1.5 fingers, incl hypothenar eminence
what is HIV-associated dementia
microglial nodules w/ subcortical dementia
involves inflammatory activation of microglial cells, which form the nodules around small areas of necrosis
describe Amyotrophic lateral sclerosis
ALS causes both UMN and LMN lesions
LMN lesion:
loss of anterior horns in spinal cord
causes muscle weakness and atrophy
UMN:
demyelination of lateral corticospinal tract
causes spasticity and hyperreflexia
mild atrophy of pre central gyrus
gene mutation in superoxide dismutatse (SOD1)
no bowel/bladder deficits
treat with Riluzole, which decreases glutamate release
describe myotonic type 1
myotonic dystrophy, autosomal dominant
caused by increased trinucleotide repeats
difficulty releasing grip from a doorknob, ex
My tonia, my testicles, my toupee, my ticker
(myotonia, testicular atrophy, frontal balding, arrhythmia)
how does Vitamin B12 deficiency present in spinal cord?
in “subacute combined degeneration” =
Spinocerebellar tract
lateral Corticospinal tracts
Dorsal columns
“back + 1 and 2” on each side = B12
presents w/ anemia, ataxia, paresthesias, impaired position/vibration, and positive Romberg
