Hepatobiliary-pancreas 1

Hepatitis
• Most common: Hep A, B, C, D, E in order
• Not nec transmitted parenterally: A, E
• Nv pd chronic carrier state: A
• E only when pregnant
• D req another infection before you can get it
• Hep A in daycare centers
• Hep A in prisons
• Hep B in IVDU (abuse)
• Hep B from needlestick accident
• HCV IgG positive – have disease now, no protective antibodies (HDV too)
• HAV, HBV (surface antibodies), HEV have protective antibodies

HBV
• Surface antigen after 1 mth of infection – asymptomatic, enzyme studies normal
• E antigen and HBV DNA are infective – next to come up
• Core IgM next to come up
• HIV positive don’t recover – chronic
• Most ppl recover: E antigen and HBV DNA disappear first, surface antigen last to
leave (first to appear)
• 6-8 wk from antigen till antibody comes up
• Surface antibody doesn’t come up till abt 1 mth after surface antigen is gone
• Core antibody IgM doesn’t leave – becomes core IgG over time
• Core IgM marker of past infection/ recovery: no surface antigen; no E antigen,
HBV DNA – not infective anymore
• If past infection: core IgG and surface antibody
• Immunized: only surface antibody
• Chronic HBV: surface antigen for more than 6 mths
• Infective vs healthy carrier: E antigen, HBV DNA positive – infective (intimate
contacts have to be immunized: can transmit sexually and IVDU)
• E antigen, HBV DNA negative, surface antigen positive: gd chance of total
recovery
• Alpha interferon therapy for infective carriers: gd chance of recovery
• Core IgG and surface antibody – long recovered
• Core IgM and surface antigen after 6 mths – healthy carrier
• Surface antigen, E antigen, HBV DNA, core IgM – infective carrier

Amoebiasis
• Entaemeba histolytica – resistant to acid (can swallow it)
• Can drill a hole through mucosa: flask shaped ulcers – bloody diarrhoea
 • Caecum drained by portal vein – org get to tributary – R lobe of liver – anchovy
paste abcess (can also drill hole through R diaphragm to lung – pd effusion –
systemic circ – go anywhere eg. brain)
• Tx: metronidazole
• Can phagocytose RBC (only amoeba that can do so)

Hydatid disease
• Definitive host: sexually active worms that have ability to lay eggs
• Intermediate host: no sexually active adults – only larval forms
• Adult – egg – larva

Sheep herder’s disease.

• Echinococcus multilocularis/unilocularis
• Sheep dog eats sheep with larval form (sheep intermediate host)
• In dog: larva becomes adult (dog is definitive host)
• Sheep herder pets dog, eggs on hand, gets into food, ingest
• Larva stays in sheep herder (intermediate host)
• Don’t want to rupture cyst: if fluid get into abdom cavity – anaphylactic shock

Tenia soleum
• Tape worm
• Larva in pig meat (intermediate host) – ingest – progress to adult (we are
definitive host)
• OR eat egg and become intermediate host – get larval form
• Cysticerci (larvae) – cystercercosis
• Larva like to go to eye and brain (esp brain) – cyst in brain, gets calcified –
seizures

Corticosteroid therapy: cataracts most common complication (not glaucoma)

Right heart failure – nutmeg liver

Thrombus in PV (prehepatic)
• No nutmeg liver (before PV empty into liver
• Ascites, potential for portal HT, varices, liver not big/congested

Thrombus in hepaticvein (posthepatic)

• Budd chiari syndrome
• Causes: polycythemia, Birth control pills
• Nutmeg liver (hepatic vein empties liver) – huge liver

Alcoholic liver disease

• Fatty change (reversible if stop drinking)
 • NADH, acetate, acetyl-CoA (make FA), fasting hypoglycemia, metabolic
acidosis, glycerol-3-phosphate (make TGs), ketone bodies, beta hydroxyl butyric
acid, etc
• Alcoholic hepatitis: Can die (if don’t stop drinking) - hepatic encephalopathy,
ascites; diff from fatty change; fever, neutrophilic leukocytosis, high enz: AST>
ALT, GGT up – systemic
• Mallory bodies: ubiquinated keratin microfilaments
• Acetaldehyde bound to a ptn: toxic compound that does the damage/cirrhosis to
liver
• Ito cell of liver: normally cell retinoic acid/ vit A in liver
• Alcoholic: acetaldehyde-ptn complex stim to make collagen tissue instead of
storing vit A – cirrhosis

Stone in common bile duct

• Cholestatis – obstruction to bile flow
• Cholesterol stone
• Liver is green
• Block bile – conj bilirubin back up into liver sinusoids
• Bilirubin in urine (water soluble)
• Light stools
• No urobilinogen in urine – conj bilirubin
• ALP and GGT elevated
• Hypercholesterolism (bile is mech of getting rid of cholesterol)
• Bile salts in skin – itching

More Cholestatis
• Bile duct radicle surrounded by fibrous tissue
• Bloody diarrhea, LLQ crampy pain
• jaundice
• IBD – UC most common cause
• Primary sclerosing cholangitis
• Lead to choriangiocarcinoma – most common cause in US (Clonorchis sinensis -
Chinese liver fluke in 3rd world country)

Even more cholestatis

• Generalized itching, not jaundiced
• 50yo woman
• Big liver
• Blood: bilirubin normal, ALP, GGT greatly increased. AST, ALT slightly
elevated
• Primary biliary cirrhosis
• Autoimmune disease
• Destruction of bile duct in portal triads
 • Not all portal triads destroyed – handle bilirubin load – no jaundice early on until
can’t handle load (late)
• Antimitochondrial antibody
• Antimicrosomal – hashimoto’s thyroiditis

Birth control pill/anabolic steroids

• Same effects in liver
• Intrahepatic cholestatis
• Jaundice
• Viral serology negative
• Transaminases normal
• ALP, GGT up
• Predispose to benign hepatic adenoma – likes to rupture: intraperitoneal
haemorrhage (will kill you)

Benign intrahepatic cholestatis

• Pregnancy – estrogen
• Goes away when baby delivered
• If jaundiced with birth control pill and goes off, will be jaundiced when pregnant

Qn
• Weight lifter
• Hypotensive, collapse
• Peritoneal tap: blood, abdomen distended
• Ruptured liver cell adenoma because he was on anabolic steroids

If on birth control pill and go off to get pregnant

• Intraperitoneal haemorrhage
• DDx: ruptured ectopic pregnancy and ruptured liver cell adenoma (and ruptured
splenic artery aneurysm)

Adult, diffusely hyperpigmented, diabetes

• Bronze diabetes (hemochromatosis)
• Iron overload disease
• Genetic: autosomal recessive (one of the most common: less than 1 in 100?)
• Instead of absorbing 10-15% in food, absorb 100% of iron
• Iron goes into cells pd hydroxyl free radicals (Fenton reaction) – free radicals do
the damage
• Target organ is liver – fibrosis and cirrhosis
• Can go to pancreas too – exocrine (malabsorption), endocrine (islet cells
destroyed - type 1 diabetes)
• Deposit in skin: iron/bronze look (combi of iron and iron stim melanocytes)
• Joints – osteoarthritis
• Pituitary – hyperpituitarism
 • Heart – restrictive cardiomyopathy

Hemosiderosis
• Acquired iron overload
• Alcoholic (lots of iron in alcohol)
• Geritol - For elderly to get iron (older people don’t need iron) - women need iron
during menses, not when old (contraindicated to take iron supplements when old)
• Cirrhosis

Cirrhosis from iron overload

• High incidence of hepatocellular carcinoma (30% +)

Screening
• Serum ferritin increased
• Serum iron high
• TIBC decreased (excess iron stores – transferrin synthesis decrease)
• % saturation increased

Tx
• Phlebotomy
• Make you iron deficient
• Don’t use chelation therapy

Von willebrand disease

• Autosomal dominant

Kayser–Fleischer rings
• Wilson’s disease
• Hepatolenticular degeneration
• Abnorm movement disorder
• Dementia
• Cirrhosis
• Autosomal recessive
• Defect in getting rid of copper and bile
• Copper builds up, accum in liver – toxic
• Over period of mths to years – chronic active hepatitis to cirrhosis
• Free copper and binding ptn to copper (ceruloplasmin) – bound and free
• 95% normal total copper level is bound to ceruloplasmin (5% free) - inactive
• Cirrhosis – not synthesizing ceruloplasmin (decrease) – free copper level increase
• Total copper level decrease (ceruloplasmin decrease), free copper level increase
• Lenticular nucleus degen
• Tx: Penicillamine – copper binder

Cirrhosis
 • Always diffused, nv focal
• Bumps: regenerative nodules
• Liver tissue is stable (G0 phase) – need to stim into cell cycle to divide
• Regen capacity – liver that grow back is not normal liver
• Only hepatocytes – no sinusoids in between, basement memb, bld vessels, no
triads, no central veins
• Regen nodules is only a pile of hepatocytes - worthless

Hepatobiliary-pancreas 2

Cirrhosis
• No triads – wall to wall hepatocytes
• Surrounded by fibrous tissues
• Micronodular: < 3mm
• Macronodular: > 3mm
• No sinusoids, etc for PV to empty bld into liver– portal HT: complications,
metabolic probs
• Pitting edema, ascites, esophageal varices related to HT
• Can’t metabolise estrogen – gynocomastia (have to feel it, can’t just look – fat
tissue) – normally 3 times in life: newborn male (estrogen effect from mother),
puberty, old age (testosterone decrease and estrogen assumes prominence)
• Palmar erythema – related to estrogen
• Spider angioma - estrogen
• Dupuytren’s contracture – most common fibromatosis (increase fibrous tissue
around tendon sheath) – common among alcoholics

Complication of ascites
• Spontaneous peritonitis in adult: E.coli (in assoc w cirrhosis)
• Child: Strep.pneumoniae

Qn
• 13 yo boy
• Unilateral mass
• Leave it alone
• Gynacomastia usually unilateral
• In women: not exactly equal breast – not respond similarly to estrogen ,
progesterone, prolactin

HCC
• Nodularity
• Almost always develops in background of cirrhosis
• Alcohol not most common cause (but most common cause of cirrhosis) – least
likely
 • More common causes: pigment cirrhosis from hemachromatosis, post-necrotic
cirrhosis of Hep B (35%) & C (30%)
• Ectopic hormones: erythropoietin
• Insulin like factors – hypoglycemia
• Secondary polycytemia
• Alpha feto protein – tumour marker

Qn
• Pt w underlying cirrhosis w ascites – stable
• Suddenly ascites gets worse
• Lose weight
• Peritoneal tap: haemorrhagic (bld in ascetic fluid – don’t assume traumatic unless
they say it)
• HCC
• Test: look for alpha feto ptn

Multiple things in tissue

• Metastasis
• In lungs but non-smoker: metastatic colon cancer (colon cancer can be due to
smoking but not most common thing)

Gall bladder disease

• Too much cholesterol and bile, too little bile salts
• Cholesterol stones
• Bile salt deficiency caused by: cirrhosis, obstruction, cholestyramine, crohn’s
disease

Qn
• 25 yo female
• RUQ crampy pain
• Fever
• Point tenderness on exam of RUQ
• Neutrophilic leukocytosis
• US: stones
• Stones not yellow – not yellow
• CBC – mild normocytic anemia
• Splenomegaly
• FHx of splenectomy
• Congenital spherocytosis: hemolyse RBC – more conjugation of bilirubin
• Supersaturated bile w bilirubin
• Calcium bilirubinate stones – jet black

Screening test for stones (gall bladder)

• US
Screening test for anything in pancreas
• CT
• Bowel overlies pancreas (US not as sensitive)

Cystic fibrosis
• Mucus: Lumen of exocrine duct blocked
• Pressure goes back to glands
• Atropy
• Malabsorption
• Can also develop diabetes (type 1)
• Fibrose off islet cells
• Genetic disease
• Chr 7 – 3 nucleotide deletion (coded for phenylalanine - missing) in CFTR ptn
• RER – GA (post translational mod): not modified – degraded instead – no CFTR
ptn, no function
• Sweat glands: normally reabsorb Na and Cl out of sweat gland – lose salt if
deficient (sweat test)
• 3yo kid, failure to thrive, chronic diarrhea, resp infections, baby tastes salty when
kiss them
• Inspisated mucus – thick in lungs, pancreas, bile ducts because CFTR in these
places don’t have usual fxn: need salt to keep it viscous (nice and lose) – but
instead Na is reabsorbed out and Cl can’t be pumped in
• Most common cause of death: infection due to pseudomonas aeruginosa
• % chance for male w CF to have children: 0-5% chance (most infertile)
• Females: can get pregnant but only 30% chance
• Cervical mucus is thick – sperms can’t penetrate through – infertile

Acute pancreatitis
• Most commonly due to alcohol
• 2nd most common due to stone that gets caught in accessory ducts
• Amylase elevated
• Epigastric pain w radiation to back – retroperitoneal organ

Qn
• After 10 days: mass in abdomen
• Pancreatic pseudocyst – a lot of fluid ard inflamed pancreas: accum and forms a
false capsule to it – build up and potential to rupture
• Amylase in peritoneal cavity

Chronic pancreatitis
• RUQ
• Dystrophic calcification (a lot)
• Alcoholic patient
 • Steatorrhea (malabsorption)
• No bile salt deficiency
• Haemorrhagic diathesis (vit K def related to malabsorption)

Carcinoma of head of pancreas

• Most common location
• Most common cause: smoking
• 2nd most common cause: chronic pancreatitis
• Painless jaundice (primarily conjugated bilirubin)
• Light coloured stools
• Palpable gallbladder (Courvoisier's sign)
• Permanently indent duodenum: barium study – duodenum looks like C on X ray
(C sign) – sign of pancreatic cancer

Acute pancreatitis
• Inflammation
• Peristalsis stops in bowel next to it just at the point next to inflammation: air in
area that didn’t peristalse (sentinel sign)
• Classic area is pancreas
• Localized ileus (lack of peristalsis) – lots of air acumm: distension

Segment of bowel distended in RLQ

• Inflammation of appendix
• Sentinel sign

Kidney
• Cast: mould of whatever is going on in nephron/ tubule – ptn that is congealing
ard whatever is present in tubule at that time – mould that is passed in urine (no
need to do a renal biopsy to see what is going on)
• GN: damaged capillaries, hematoria, rbcs in nephron trapped in cast
• Renal tubular necrosis: tubules sloughing off – renal tubular cast
• Acute pyelonephritis: neutrophils infiltrating tubules and tissues – cast of
neutrophils (wbc casts) – infection in kidney
• Lipid in urine in nephritic syndrome: cast of fat (fatty cast)
• First thing that disappears with renal failure: ability of kidneys to conc urine
• Even before BUN and creatinine have even increased, even before there are any
renal tubular casts
• Specific gravity of urine after overnight sleep: can tell you if conc or dilute urine
(greater than 1.023 = pt concentrating urine, kidneys normal)
• 1.010 = hypotonic, pt can’t conc, renal failure
• Hyaline cast: cast of ptn (most of the time means nth, other casts have
significance)
• Crystals: uric acid (urine has to have acid pH to form uric acid crystal); pt w gout,
want to stop uric acid crystals, alkalinize urine (using carbonic anhydrase
 inhibitor – block bicarb reclamation alkalinize urine and prevent crystal
formation)
• Calcium oxalate crystals: pt drank ethylene glycol (stupor state, increased anionic
gap, metabolic acidosis, crystals in urine)
• Calcium oxalate stones are the most commonly passed

Pathology
• Horseshoe kidney: inferior mesenteric artery restrict movement
• Artery goes over it and traps kidney from behind it
• Prevents it from desc/asc

Cystic diseases of the kidney

• Infantile polycystic kidney disease: autosomal recessive (present at birth)

• Kidneys both polycystic
• Oligohydramnios
• In amniotic sac w hardly any amniotic fluid ard it
• Malformations related to pressure
• Potter’s facies – sign of oligohydramnios in a child w polycystic kidney
• Can’t breathe – lungs are hypoplastic (can’t fill them up enough)
• Cysts also in liver, pancreas
• Incompatible w life

• Adult polycystic kidney disease: autosomal dominant (cysts not present at birth,
come up at 10, 11, 12 years of age)
• delayed manifestation
• penetrance: have the abnormality when u look at the gene but don’t have any
cystic disease (never express genetic abnormality in your life)
• but can transmit it to your kids
• hard to recognize on a pedigree (Marfan’s is a classic eg. Abnormality on chr 15
but normal looking, pass on to kids – incomplete penetrance); (familial polyposis
has 100% penetrance: you have the gene, you have the disease)
• develop HT – predispose to bleeds in brain (standard kind with HT: charcot-
bouchard aneurysms [small bld vessels] – rupture OR ruptured berry aneurysm
[larger bld vessels]: brain covered with blood – get into subarachnoid space)
• bld in subarachnoid space: worst headache you will ever have

Qn
• high assoc w mitral valve prolapse
• HT, abnormality in US in renal pelvis area
• Click murmur
• APKD cause of HT
Qn
• High incidence of diverticulosis in pts w APKD
• Lost 600ml of blood all of a sudden
• HT, abnorm in US of renal area
• Diverticulosis is most common cause of hematochezia (maroon coloured stools)

Glomeruloneprhitis
• -itis: type 3 hypersensitivity reaction
• Lipoid nephrosis, FSGS, diabetic glomerular sclerosis – not immune disease
• IgA GN, diffuse membranous GN – yes
• Diffuse: every single glomerulus has smth wrong w it
• Focal: not all glomeruli are involved
• Disease is focal and disease in glomerulus is focal: focal segmental
• Proliferative: lots of them; more than 100 nuclei in glomerulus consistently –
proliferative type GN, in all of them – diffuse proliferative GN
• Not a lot of dots, thick memb: membranous
• Thick memb and lots of dots: membranal proliferative GN

Renal 1

Schematics
• Visceral epithelial cells – have feet: podocytes
• Spaces between ‘feet’ – slit pore
• Blood, endothelial cells, basement memb (made by podocytes), visc epi cells,
parietal epi cells (line bowman’s capsule)
• -ve charge of BM keeps albumin out of urine (glycosaminoglycan: heparan
sulfate)
• If damage visc epi cells, also damage BM: lots of ptn in urine – nephrotic
syndrome: >3.5g/24 hrs
• Test on renal biopsies: stains (silver, H&E, etc), IF stains (linear or
granular/lumpy bumpy pattern)
• Patterns: Immune Complexes or antibodies that are detected
• EM tells us where these are deposited
• EM can tell if podocytes are fused
• Eg. IgG anti-BM antibody - in blood, into glomerular capillary, directed against
BM, IgG antibody lines along it, fluorescent tag will show an outline of all BM in
glomerulus (linear pattern): Goodpasture’s syndrome
• IC: antigen and antibody attached – circ in bloodstream
• Eg. Lupus: antigen is DNA, antibody is anti-DNA, attach to each other, travel in
bldstream, deposit somewhere (eg. Glomerular capillary) – type 3 hypersensitivity
• Larger than individual antibodies: bigger, diff solubilities, diff charges, not
deposit in nice neat fashion in glomerulus (location depend on size, charge)
• If under endothelial cell nucleus – subendothelial deposit (so big, it can’t get
through BM and under podocyte)
 • Post-streptococcal GN – bacterial antigen and antibody against it: v small,
soluble, can go through BM – deposit under epithelial side (subepithelial deposit)
• Can see under EM (electron dense) but not w IF
• Diff solubilities, diff charges
• IgA GN is the only GN you can diagnose w IF
• Granular – IC type 3 disease
• Anti-BM antibodies: type 2 not type 3

GN
• 2 types: nephritic or nephritic
• One can become another (nephritic to nephritic)
• Nephritic: unique cast (rbc cast) HEMATURIA, inflam of glomerulus - ptn
<3.5g/24 hrs (if dead, nephrotic) - MILD TO MOD PROTEINURIA (spilling
ptn but not same lvl as nephritic syndrome) – no pitting edema/ascities;
OLIGURIA (GFR decrease), decrease sodium reabsorption, not filtering as much
sodium – sodium builds up (HT)
• Nephritic: fatty cast, 3.5g ptn /24 hr sample, pitting edema (lost that much ptn)
• Most of the time doesn’t go from nephritic to nephrotic but it does happen
• Proliferative GN: too many nuclei
• Eg. Patient haad scarlet fever 1 wk ago, hematuria, mild to mod proteinuria,
oliguria, HT, periorbital puffiness (due to retaining salt) – post-streptococcal GN
• EM: IC (bacterial antigen-antibody) – denser than BM, close to epithelial side
(subepithelial deposits) - post-streptococcal GN
• Tx: corticosteroid therapy
• Can come back every now and then but it goes away

Qn
• 35 yo woman
• Positive Serum ANA: ring pattern (anti-double stranded DNA antibody present)
• Lupus – almost always involves kidneys
• 6 diff types
• Type 4 most common: diffuse proliferative GN – most common overall one seen
in lupus
• Wire loops
• EM: black stuff in BM - DNA-antiDNA immune deposits (subendothelial)

Nephrotic syndrome
• Split pores fused

Crescentic GN
• Glomerulus surrounded by bunch of proliferative cells (parietal epi cells)
• Looks like crescent around it
• Worst GN to have – within 3 mths, acute renal failure and die unless on dialysis
 • Many diseases can have this but the only one to know is goodpasture’s syndrome
(still nephritic) – see crescents in biopsy (bad prognosis)
• Other: polyarteritis nodosa, wegener’s gralunomatosis

Maltese crosses
• Cholesterol in urine
• Pathognomonic cast of nephrotic syndrome

Nephrotic syndrome
• >3.5g/24 hrs
• Presence of fatty cast in urine
• Ascites/pitting edema
• Run the risk of spontaneous peritonitis: if kid, org is Strep pneumoniae, if adult,
E.coli

Qn
• EM from 8yo w URI 1 wk ago
• Diffusely has pitting edema all over body, ascites
• Anasarca – edema all over
• Normotensive
• Did renal biopsy (don’t do anymore), H& E stain, IF
• Normal appearing glomerulus
• Rbc in glomerular capillary lumen on EM
• No electron dense deposits on basement membrane
• Podocytes fused except at one point
• Fusion of podocytes in any cause of nephrotic syndrome
• Maltese crosses
• Lipoid nephrosis

Nephrotic syndrome patients

• Albumin low, liver makes more cholesterol, but nobody knows why
• Hypercholeterolaemia
• Cholesterol can’t get into urine because they have glomerular disease – casts w
cholesterol (looks like maltese crosses)
• Lipoid nephrosis (minimal change disease)
• Lose negative charge in glomerular BM– albumin can get through, selective
proteinuria (only albumin increase in urine - >3.5g/24 hr)
• Treat with corticosteroid in a few months, remission
• Might come back
• After abt a year, goes away nv to come back again
• Most common cause of nephritic syndrome

HIV positive patient

• AIDS
 • Pitting edema
• Urine >3.5g/24 hr
• Fatty casts
• HT
• Biopsy: some glomeruli normal, some abnormal, only a part of glomerulus – focal
segmental glomerulosclerosis (most common glomerular lesion in AIDS patients
and intravenous drug abusers – next to rapidly progressive crescentic
glomerulonephritis)
• EM: electron dense deposits

Qn
• Adult, pitting edema, fatty cast, >3.5g/24 hr
• Biopsy: number of nuclei less than 100 (not proliferative), thick basement memb
• Diffuse membranous glomerulonephritis – most common cause of nephrotic
syndrome in adults
• Subepithelial in EM
• Silver stains magnified: hair on end appearance/ epi-membranous spikes
(immunocomplexes under silver stain)
• Drugs (non-steroidals, captopril – treat HF, diabetic nephropathy), infection (Hep
B, P.malariae, syphilis), cancer (colon cancer, anti-CEA antibodies), idiopathic
causes
• Can die unless renal transplant

Type 1& 2 membrano-proliferative glomerulonephritis

• Immune complex (-itis)
• Type 1 has relationship w Hep C
• Membranous – Hep B (Hep B also related to polyarteritis nodosa – a vasculitis)
• Membranous-proliferative - Hep C (Hep C also related to cryoglobuminemia)
• Type 1: subendothelial deposit, pd nephrotic syndrome
• Type 2: less common, autoantibody against C3 (C3 nephritic factor) – causes C3
convertase to become overactive – constantly breaking complement down (lowest
complement levels in any glomerulonephritis seen here) – dense deposit disease
(entire BM is an immune complex)

Tram tracks
• mesangial cells extending itself between BM and endothelial cell – look like a
tram track
• tram tracking membranoproliferative nephrotic syndrome

Diabetic glomerulosclerosis
• big round ball on H&E stain

hyaline arteriolosclerosis
• small vessel disease w diabetes and HT
 • first vessel to be hyalinised is efferent arteriole
• if lumen narrow, GFR increased
• creatinine clearance increased
• early diabetic nephropathy – increased creatinine clearance and GFR cuz efferent
arteriole hyalinised and obstructed.
• Hyperfiltration damage

Non-enzymatic glycosylation
• Glucose attach to aa in a ptn
• Also going on in above cuz pt not washing themselves
• Non-enzymatically glycosylating glomerular BM
• BM permeable to protein
• Pressure + glycosylation = spill ptn into urine (microalbuminuria)
• Standard dipstick for ptn will not detect these
• Give ACE I – stop progression of this
• Afferent arteriole caliber controlled by PGE2
• Efferent arteriole caliber controlled by angiotensin II (normally constricts it)
• Give ACE I – decrease Ang II, take off vasoconstrictive element – take off
pressure off glomerulus, decrease GFR, decrease damage from constant pounding
on glomerulus
• Have to get gluc into normal range (ACE I not prevent that) – need perfect
glycemic control from now on (under 6%) – otherwise chronic renal disease
• ACEI prevent progression of disease
• Diabetics commonly have HT – ACEI control HT

Type IV collagen in mesangium

• Forms big circles
• Pink
• Hyaline arteriole sclerosis – diabetic kidney
• Builds up in pts w diabetes
• Diabetic glomerulosclerosis
• Kimmelstiel-Wilson disease
• Nodular glomerulosclerosis

Amyloid
• Deposit in kidneys
• Special ptn
• Stain w congo red and polarize it – apple green birefringence (like granny smith
apple)
• Assoc w nephrotic syndrome

IgA glomerulonephritis
• Most common one
• Berger’s disease
• Variant (if not the same as) Henoch–Schönlein purpura (hematuria and rbc casts)
• Anti IgA antibodies
• More nephritic than nephrotic
• IF – all of it is taken up in mesangium (where IC are)
• Episodic episodes of gross hematuria in kids, goes away, may come back maybe a
couple of years later
• In adults: may present as episodic bouts of microscopic hematuria
• Hematuria, rbc casts, little bit of proteinuria, no HT
•