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SUGER Flashcards

1
Q

where does normal proliferation of the skin occur?

A

just in basal layer

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2
Q

what are the functions of the skin?

A

barrier to infection

thermoregulation

protection against trauma and UV

vitamin D synthesis

regulate H2O loss

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3
Q

layers of the skin

A

epidermis, dermis, subcutaneous tissue

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4
Q

what is the epidermis?

A

outermost layer - stratum corneum

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5
Q

what is the epidermis made of?

A

corneo-desmosomes and desmosomes

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6
Q

what do corneodesmosomes do?

A

adhesion molecules

keep corneocytes together

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7
Q

when are increased numbers of corneodesmosomes seen?

A

psoriasis - thickening of the stratum corneum

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8
Q

when are decreased numbers of corneodesmosomes seen?

A

atopic eczema - thinning of stratum corneum, increased risk of inflammation

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9
Q

what does a healthy skin barrier consist of?

A

filaggrin, corneocytes

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10
Q

what does filaggrin do?

A

derived from profilaggrin (structural component of the cornfield envelope)

produces natural moisturising factor

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11
Q

what are corneocytes filled with? why?

A

NMF

maintain skin’s hydration, keeps H2O inside the skin

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12
Q

what is NMF? what does it do?

A

natural moisturising factor

maintain skin hydration, keep NMF inside skin

maintain acidic environment at outer surface of the stratum corneum

filled with acids

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13
Q

what is desquamation?

A

mature corneocytes are shed from the surface of the stratum corneum

balance introduction of new cells in basal layer

degradation of extracellular corneodesmosomes under protease enzymes

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14
Q

what enzymes are involved in desquamation?

A

proteases - degradation of extracellular corneodesmosomes

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15
Q

what is the pH of normal skin? what does this allow?

A

5.5

proteases remain on skin - enables balance of new cells from basal layers

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16
Q

what does lipid lamellae do?

A

keeps water inside skin cells

irritants/allergens bounce off surface of skin

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17
Q

what is the brick wall model?

A

corneocytes are the bricks, corneodesmosomes are the iron rods and lipid lamellae is the cement

iron rods only rusty near surface of skin barrier

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18
Q

what is the role of vitamin D in the skin?

A

producing the anti-microbial peptides needed to defend the skin from bacteria and viruses

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19
Q

what do irritants and allergens do?

A

irritants break down healthy skin

allergens trigger flare ups by penetrating into the skin and causing it to react

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20
Q

skin flare ups

A

caused by allergens - met with lymphocytes which release chemicals to induce inflammation

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21
Q

types of inflammation

A

red skin - dilation of blood vessels

itchy skin - stimulation of nerves

dry skin - skin cells leaking

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22
Q

cause of increased pH on skin

A

profilaggrin and filaggrin aren’t present - lack of NMF, so less water retention in corneocytes

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23
Q

effect of increased pH on skin

A

due to less water retention in corneocytes

damage to skin barrier as corneodesmosomes are damaged -> breakdown of skin and increased risk of infection

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24
Q

what happens in acne?

A

hypercornification

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25
Q

what does hypercornification lead to?

A

corneodesmosomes blocking entrance to hair follicles

increased production of sebum by sebaceous glands

sebum trapped in narrow hair follicle

sebum stagnates at pit of follicle where there’s no oxygen

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26
Q

what does the stagnation of the sebum lead to?

A

anaerobic conditions -> propionic bacteria acnes (p.acnes) multiply in stagnant sebum

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27
Q

what do p.acnes do?

A

breakdown triglycerides in sebum into FFAs -> irritation, inflammation, neutrophils

pus formation and further inflammation (follicle filled with neutrophils)

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28
Q

what is cosmetically induced acne?

A

cosmetics and oily hair gel can trigger acne - help plug hair follicle and initiate acne process

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29
Q

where are the kidneys? what are they derived from?

A

retroperitoneal

mesoderm

T12 - L3

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30
Q

right kidney vs left position

A

right kidney is lower than left

pushed down by liver

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31
Q

where are the hilums of the kidneys?

A

right: L2
left: L1

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32
Q

distinct structures of the kidneys

A

cortex, medulla and pelvis

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33
Q

what does the medulla consist of?

A

20 upside down pyramids

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34
Q

what does the pelvis contain?

A

fat and urine collecting system

transitional epithelium

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35
Q

what does the cortex contain?

A 
renal corpuscules (glomerulus and bowman's capsule) and PCT/DCT
medullary ray
interlobular artery
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36
Q

what is the medullary ray?

A

collection of loop of Henle tubules

collecting ducts

striated appearance

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37
Q

what does the medulla contain?

A

no renal corpuscules

no glomeruli

tubules of loop of Henle, collecting duct and blood vessels

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38
Q

how are tubules in the medulla orientated?

A

radially - point from cortex to medulla

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39
Q

what is the renal pelvis?

A

space that urine drains into -continuous with collecting ducts proximally and ureters distally

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40
Q

what is the renal pelvis lined by?

A

transitional - same as in bladder

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41
Q

where does the renal artery come off?

A

abdominal aorta at L1

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42
Q

division of renal artery

A

into segmental arteries and suprarenal arteries, lead to radial network of arcuate arteries

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43
Q

what do arcuate arteries divide into?

A

travel circumferentially at the junction between cortex and medulla

give off interlobar arteries

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44
Q

what do interlobar arteries supply and divide into?

A

each lobe (medullary pyramid and overlying cortex) and divide into interlobular arteries

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45
Q

what do interlobular arteries divide as?

A

afferent arterioles

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46
Q

basic functions of the segments of the nephron

A

renal corpuscle - filter

proximal convoluted tubule -reabsorbing solutes

loop of Henle - concentrating urine

distal convoluted tubule - reabsorbing more water and solutes

collecting duct - reabsorbing water and controlling acid base and ion balance

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47
Q

what is the renal corpuscule?

A

whole unit of the glomerular tuft and bowman capsule

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48
Q

how thick is the urothelium?

A

5 cells

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49
Q

what does the surface layer of the glomeruli consist of?

A

large dome-shaped umbrella cells

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50
Q

what are umbrella cells?

A

large and cover several underlying intermediate cells

tight junctions to prevent urine going between cells, keep apical membrane components from diffusing to lateral aspects of cells, prevent material diffusing around cells

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51
Q

basal layer of urothelium

A

cuboidal cells

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52
Q

layers of bladder epithelium

A

surface, intermediate and basal layer

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53
Q

do ureters have serosa?

A

no

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54
Q

how is urine propelled along the ureter?

A

peristalsis

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55
Q

layers of the bladder

A

lamina propria, muscularis mucosa, submucoas, muscularis propria, subserosa/serosa

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56
Q

what prevents reflux into the ureter from the bladder?

A

functional valve

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57
Q

what sphincters are in the urethra? what do they do?

A

internal - smooth muscle from the bladder

external - skeletal muscle from the pelvic floor

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58
Q

total renal blood flow

A

1L/min

meet their metabolic demands and filter/excrete waste

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59
Q

total urine flow

A

1ml/min

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60
Q

divisions of renal artery

A

renal artery, segmental, interlobar, arcuate, interlobular, afferent arteriole, glomerular capillary, efferent arteriole, peritubular capillary

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61
Q

how much plasma filters into Bowman’s capsule from the blood?

A

20%

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62
Q

layers of the glomerular filtration barrier

A

single-celled capillary endothelium

BM

single-celled epithelial lining of Bowman’s capsule (podocytes)

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63
Q

how does fluid filter through the GFB?

A

across endothelial cells

BM

between foot processes of podocytes

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64
Q

what do efferent arterioles supply?

A

peritubular capillaries (supply proximal and distal convoluted tubules)

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65
Q

how is a baby’s skin different to adult skin?

A

baby skin has naturally thin brick wall

needs very little damage, allergens could break through

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66
Q

why does atopic dermatitis start in babies?

A

thin brick wall

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67
Q

why does AD start on the face?

A

thin stratum corneum

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68
Q

epidermal barrier in normal vs eczematous skin

A

thinner stratum corneum

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69
Q

genetic susceptibility of AD

A

changes in filaggrin gene -> less NMF and water

degradatory proteases -> degraded corneodesmosomes

abnormal cornified envelope

breakdown lipid lamellae

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70
Q

environment interacting with genetics in AD

A

soaps/harsh detergents can raise pH of skin, breaking barrier

generates sub-clinical inflammation -> mild AD (intrinsic)

dust mite (produces proteases and acts as allergen)

staphylococcus aureus

saliva, breast milk, nasal secretions, foods, friction

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71
Q

what does inflammation do to filaggrin?

A

down regulates it

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72
Q

what do allergens do?

A

Th1 -> Th2, leading to inflammatory response

NA -> allergic

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73
Q

what is sensitisation?

A

babies develop allergies not through eating, but through topical application

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74
Q

what is tolerance induction?

A

giving food early can prevent allergy to it later on

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75
Q

what is the atopic march?

A

first AD, then allows food to get in (food allergy) which changes the immune system to Th2, which can lead to asthma

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76
Q

what chemical messengers does damaged skin release?

A

cytokines (IL-1, TSLP, IL-25, IL-33) trigger immune system, leads to skin barrier suppression, eosinophilia, pru

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77
Q

effect of inflammation the brain

A

IL-1, IL-6, TNFalpha increases 5 HTTP, leading to decreased serotonin which can decrease melatonin and depression/anxiety

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78
Q

what is disease modification?

A

change disease forever

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79
Q

how can we repair the skin barrier in AD?

A

foundation: emollients to repair barrier

irritants and allergen avoidance

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80
Q

what do lipid bilayers do?

A

prevents water loss

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81
Q

what do occlusive emollients do?

A

trap moisture in skin - transiently increase hydration

artificial barrier above stratum corneum

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82
Q

humectants

A

help retain moisture in skin

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83
Q

why are emollients sometimes not effective?

A

used in minimal quantities

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84
Q

what proportion does non-compliance leading to therapeutic failure occur?

A

50%

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85
Q

what is the greatest response in the treatment of AD?

A

education

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86
Q

what is eczema herpeticum?

A

herpes simplex 1 or 2

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87
Q

what do people with AD want?

A

time to listen, explain and demonstrate

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88
Q

steps of AD management

A

complete emollient therapy

treatment of flareups

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89
Q

role of vit D in skin barrier

A

filaggrin, dysregulation of AMP LL37, abnormal ceranide levels in lipid lamellae

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90
Q

what shifts Th0 to Th2?

A

prostaglandins from histamine released by mast cells and basophils

IL-4

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91
Q

what does dupilumab do?

A

prevents IL-4 from producing excess IgE

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92
Q

what is HbA1c?

A

glycated haemoglobin

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93
Q

what does HbA1c identify?

A

average plasma glucose concentration

by measuring it, we can see what our average blood sugar levels have been over weeks/months

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94
Q

when does HbA1c develop?

A

when haemoglobin joins with glucose in the blood - becomes glycated

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95
Q

HbA1c in diabetes

A

the higher the HbA1c, the greater the risk of developing diabetes-related complications

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96
Q

how does HbA1c return an accurate average measurement of average blood glucose?

A

when body processes sugar, glucose naturally attaches to Hb

amount of glucose that combines with Hb is directly proportional to the total amount of sugar in system

long term measurement due to erythrocyte lifespan

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97
Q

what is the HbA1c target for diabetes patients?

A

48 mmol/mol (6.5%)

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98
Q

HbA1c vs blood glucose level

A

HbA1c provides a long-term trend of how high blood sugars have been over a period of time

blood glucose level is the conc. of glucose in blood at a single point in time

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99
Q

how often should HbA1c be tested?

A

at least once a year

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100
Q

what is CKD?

A

chronic kidney disease

long term condition where kidneys don’t work as well as they should

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101
Q

in who is CKD more common?

A

black people and people of south Asian origin

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102
Q

symptoms in early CKD

A

usually no symptoms

may be picked up if blood/urine tests pick up problems

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103
Q

symptoms in advanced CKD

A

tiredness, swollen ankles/feet/hands, SOB, feeling sick, blood in urine

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104
Q

causes of CKD

A

often by other conditions that put a strain on the kidneys

high BP, diabetes, high cholesterol, kidney infections, glomerulonephritis, polycystic kidney disease, blockages in urine flow, lithium/NSAIDs

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105
Q

medication for CKD

A

none specifically for CKD, but they’re used to control conditions causing it

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106
Q

control of BP in CKD

A

aim for below 140/90, below 130/80 in diabetes

ACE inhibitors used, e.g. Ramipril, enalapril, lisinopril

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107
Q

control of cholesterol in CKD

A

higher risk of cardiovascular disease

statins e.g. atorvastatin, fluvastatin and simvastatin

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108
Q

side effects of statins

A

headaches, feeling sick, constipation/diarrhoea, muscle and joint pain

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109
Q

control of water retention in CKD

A

kidneys can’t remove fluid -> oedema

reduce salt/fluid intake, diuretics e.g. furosemide

side effects: dehydration and hypokalemia/hyponatremia

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110
Q

control of anaemia in CKD

A

later-stage kidney disease - anaemia often developed

injections of erythropoietin/iron supplements

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111
Q

bone problems in CKD

A

severely damaged kidneys -build-up of phosphate in body as kidneys can’t get rid of it

important for maintaining bone health, but a too much can upset calcium balance

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112
Q

control of bone problems in CKD

A

limit high phosphate foods
phosphate binders - calcium acetate and calcium carbonate

vit D - colecalcifeol/ergocalciferol

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113
Q

glomerulonephritis in CKD

A

medicine to reduce activity of immune system, e.g. steroids or cyclophosphamide

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114
Q

what does dialysis do?

A

removes waste products and excess fluid from the blood

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115
Q

what types of dialysis are there?

A

haemodialysis and peritoneal dialysis

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116
Q

what is haemodialysis?

A

diverting blood into an external machine, where it’s filtered then returned to the body

3 times a week

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117
Q

what is peritoneal dialysis?

A

pumping dialysis fluid into abdomen to draw out waste products

several times a day/overnight

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118
Q

what determines fetal sex?

A

SRY gene switches testicular development

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119
Q

what does the SRY gene do?

A

switches testicular development

testes produce MIF

prevents Muellerian duct development

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120
Q

what happens in absence of Y?

A

ovaries and Mullerian ducts form

uterus and fallopian tubes form

two X chromosomes required

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121
Q

what are germ cells?

A

specialised cells that develop into gametes

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122
Q

where do germ cells migrate to?

A

genital ridge by amoeboid movement

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123
Q

when does mitotic division occur?

A

rapid, until 20 weeks

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124
Q

what is the kidney surface anatomy?

A

retroperitoneal

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125
Q

where is the kidney derived from?

A

mesoderm

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126
Q

nephron in the cortex, medulla and pelvis

A

cortex: proximal and distal convoluted tubules and renal corpuscles
medulla: loop of Henle and collecting ducts
pelvis: receives collecting ducts

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127
Q

what do the renal corpuscles consist of?

A

glomerulus and Bowman’s capsule

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128
Q

how many nephrons do we have?

A

2 million in total - one in each kidney

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129
Q

what does the proximal tubule consist of?

A

proximal convoluted tubule and proximal straight tubule

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130
Q

what does the loop of Henle consist of?

A

descending limb of loop of Henle, thin segment of ascending limb of loop of Henle and thick segment of ascending limb of loop of Henle

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131
Q

what does the collecting duct system consist of?

A

cortical collecting duct and medullary collecting duct

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132
Q

histology of the renal corpuscle

A

tuft of convoluted tubules with fenestrated walls

glomerular tuft supported by smooth muscle mesangial cells

outside glomerular capillaries is the BM

on opposite side of glomerular BM are podocytes

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133
Q

what is the glomerular tuft supported by?

A

smooth muscle mesangial cells

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134
Q

what is outside the glomerular capillaries?

A

glomerular BM

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135
Q

what is on the opposite side of the glomerular BM?

A

layer of cells called podocytes

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136
Q

what does the glomerular BM consist of?

A

fusion of 2 BMs: capillary BM and podocyte BM

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137
Q

what is the most proximal part of the urinary tract?

A

Bowman’s capsule - continuous with proximal convoluted tubule downstream

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138
Q

how can you distinguish mesangial cells from the capillaries?

A

stain tissue with PAS

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139
Q

PAS in kidneys

A

stains glycoproteins in glomerular BM - highlighting capillaries and allowing you to see mesangial cells inbetween

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140
Q

what are mesangial cells?

A

modified smooth muscle cells

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141
Q

what are the functions of mesangial cells?

A

structural support for the capillary and production of extracellular matrix protein

contraction of them in the glomerulus tightens capillaries and reduces GFR - important in tubuloglomerular feedback where chemical changes in tubules feedback to alter GFR

involved in phagocytosis of the glomerular filtration membrane breakdown products

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142
Q

how are mesangial cells important in tubuloglomerular feedback?

A

their contraction tightens capillaries and reduces GFR - chemical changes in the tubules feedback to alter GFR

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143
Q

what are the components of the juxtaglomerular apparatus?

A

afferent arteriole and distal convoluted tubule

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144
Q

how are granular cells formed? what do they do?

A

endothelium of the afferent arteriole is expanded to form mass of cells (granular cells)

detect BP and secrete renin in response to a reduction in BP

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145
Q

when do granular cells secrete renin?

A

reduced BP

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146
Q

what is the macula densa? what does it do?

A

distal convoluted tubule closely aligned to glomerulus and afferent arteriole

expansion of cells at juxtaglomerular apparatus - macula densa

detect sodium levels

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147
Q

what does the macula densa do when filtration is slow?

A

more sodium is absorbed, and macula densa sends signal to reduce afferent arteriole resistance and increase GFR

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148
Q

what is another group of cells in the juxtaglomerular apparatus?

A

Lacis cells

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149
Q

what is the proximal convoluted tubule lined by?

A

cuboidal epithelium

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150
Q

what are the characteristics of the cells in the proximal convoluted tubule?

A

microvilli - increase SA of cell (fuzzy surface)

increased SA increases absorptive capacity of the cell

many mitochondria for active transport - 2/3 of sodium and potassium

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151
Q

why do cells of the proximal convoluted tubule have a fuzzy surface?

A

cells have microvilli

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152
Q

what does the proximal convoluted tubule absorb/resabsorb?

A

actively transport ions from filtrate including 2/3 of sodium and potassium

absorb small protein molecules that got through the glomerulus

reabsorption of NaCl, proteins, polypeptides, amino acids and glucose

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153
Q

what are the black dots in the proximal convoluted tubule? what do they do?

A

lysosomes - degradation of small protein molecules absorbed from urinary space

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154
Q

which convoluted tubule has more lysosomes?

A

proximal

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155
Q

what are the thin segments of the ascending and descending limbs of the loop of Henle lined by?

A

simple squamous

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156
Q

what are the thick segments of the ascending and descending limbs of the loop of Henle lined by?

A

low cuboidal

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157
Q

what is the loop of Henle supplied by?

A

rich vasa recta

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158
Q

how do the loops of Henle travel?

A

each loop dips down far into the medulla and then returns to form the distal convoluted tubule and return to the same nephron it left

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159
Q

what does the loop of Henle transport/receive?

A

water but not ions passively flow out of the thin descending limb into the high osmolarity interstitium - concentrates urine

ions the body wants back are actively pumped out of the ascending limb, leaving water and waste products

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160
Q

how is the urine concentrated in the loop of Henle?

A

water but not ions passively flow out of the thin descending limb into high osmolarity interstitium

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161
Q

what is left in the ascending limb of the loop of Henle?

A

after the ions the body wants back are actively pumped out, water and waste products are left

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162
Q

why is the loop of Henle deep in the medulla prone to ischemia?

A

vasa recta are quite far from glomerulus (where afferent arteriole enters to supply O2) so before blood has reached it, it’s already lost some of the oxygen it was carrying

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163
Q

what is ischemia?

A

temporary loss of blood supply/inadequate blood supply

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164
Q

how is the histology of the distal convoluted tubule different to the proximal one?

A

cells don’t have microvilli - no fuzzy brush border

much shorter - looking at a section of cortex, you’d see more proximal tubule

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165
Q

cells of the distal convoluted tubule

A

cuboidal

mitochondria

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166
Q

what does the distal convoluted tubule do?

A

regulating acid-base balance

acidifies the urine by secreting H+ ions into it (derived from intracellular carbonic anhydrase)

exchanges urinary Na+ for body K+ (mediated by aldosterone)

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167
Q

how does the distal convoluted tubule acidify the urine?

A

secreting H+ ions into it -derived from intracellular carbonic anhydrase

regulates acid-base balance

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168
Q

what process in the distal convoluted tubule is mediated by aldosterone?

A

exchanging urinary Na+ for body K+

can lead to hypernatraemia and hypokalaemia

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169
Q

what is the collecting duct lined by?

A

cuboidal epithelium

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170
Q

what is the cuboidal epithelium made up of?

A

2 cell types: principal and intercalated cells

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171
Q

what do the principal cells in the collecting ducts do?

A

respond to aldosterone (exchange Na+ for K+) and ADH (increasing water reabsorption by insertion of Aquaporin-2 into apical membrane

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172
Q

what does ADH do?

A

increase water reabsorption by the insertion of Aquaporin-2 into the apical membrane of the cell

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173
Q

what is Aquaporin-2? where is it inserted into?

A

membrane channel for water reabsorption in the collecting duct

apical membrane of the cell

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174
Q

what can cause diabetes insipidus?

A

mutation in the AQP2 gene (aquaporin-2 gene)

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175
Q

what is AQP2? where is it located?

A

provides instruction for making aquaporin 2 protein

12q12.12

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176
Q

what does mutation of the AQP2 gene usually cause?

A

aquaporin 2 protein is misfolded into an incorrect 3D shape

misfolded protein trapped within the cell, where it can’t reach the membrane to transport water molecules

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177
Q

what is nephrogenic diabetes insipidus?

A

disorder of water balance - produce too much urine (polyuria), causing them to be excessively thirsty (polydipsia)

acquired or hereditary

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178
Q

what do intercalated cells do?

A

exchange acid for base (both ways)

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179
Q

what types of intercalated cells are there? what do they do?

A

alpha intercalated cells secrete acid

beta intercalated cells secrete bicarbonate

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180
Q

how can collecting ducts be recognised?

A

plumper epithelium than the loop of Henle with a round central nuclei

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181
Q

what is the renal pelvis lined by? what does it do?

A

transitional epithelium (urothelium)

transmits filtrate from nephron to the ureters

collecting duct drains into it

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182
Q

what are the ureters lined by?

A

transitional epithelium

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183
Q

what are the muscles of the ureter?

A

spiral muscular tubes:
inner - longitudinal
outer - circular

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184
Q

what is the structure of the ureter?

A

no serosa

loose adventitia

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185
Q

how is urine propelled along the ureter?

A

peristalsis

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186
Q

what is the bladder lined by?

A

transitional epithelium

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187
Q

what are the layers of the bladder?

A

lamina propria, muscularis mucosa, submucosa, muscularis propria, subserosa and serosa

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188
Q

what does the bladder contain to prevent reflux into the ureter?

A

functional valve

189
Q

what are the sphincters in the urethra?

A

internal: smooth muscle from the bladder
external: skeletal muscle from pelvic floor

190
Q

what is the structure of the female urethra?

A

4-5cm long

proximally transitional epithelium

distally squamous epithelium

191
Q

what is the structure of the male urethra?

A

20cm long

prostatic urethra, membranous urethra (transitional epithelium) and penile urethra (pseudostratified epithelium proximally and stratified squamous epithelium distally)

192
Q

what are the functions of the kidney?

A

endocrine function

maintain balance of salt, water and pH

excrete waste products

193
Q

how much of the CO does each kidney receive?

A

20%

194
Q

what is total renal blood flow? what is this for?

A

1L/min (both kidneys)

meet own metabolic demands and filter/excrete metabolic waste products of the whole body

195
Q

what is the total urine flow?

A

1ml/min

196
Q

where are the capillary beds of each nephron?

A

glomerulus and peritubular area

197
Q

what connects the 2 capillary beds in the nephrons?

A

efferent arteriole (blood leaves glomerulus)

198
Q

afferent vs efferent arterioles

A

afferent arteriole comes before efferent arteriole as A comes before E

199
Q

why is the renal circulation unusual?

A

includes 2 sets of arterioles and 2 sets of capillaries

200
Q

what is the sequence of blood supply of the nephron?

A

afferent arteriole comes off of interlobular artery, then becomes the glomerular capillary, then the efferent arteriole, then the peritubular capillary, which join to forms where blood leaves the kidneys

201
Q

what occurs in the peritubular capillary?

A

tubular secretion and tubular reabsorption

202
Q

what does the renal corpuscle form?

A

filtrate from the blood that is free of cells, larger polypeptides and proteins

203
Q

what is the filtrate free of? what happens to it?

A

free of cells, larger polypeptides and proteins

leaves renal corpuscle and enters the tubule

substances are added/removed from it

204
Q

what forms the urine?

A

fluid remaining at the end of each nephron combines in the collecting ducts and exits the kidneys as urine

205
Q

what is Bowman’s capsule?

A

fluid filled capsule

206
Q

what constitutes the renal corpuscle?

A

glomerulus and Bowman’s capsule

207
Q

how does blood leave the glomerulus?

A

efferent arteriole

208
Q

what is the Bowman’s capsule covered by?

A

parietal epithelium

209
Q

what filters into Bowmans space?

A

within capsule

protein free fluid filters from glomerulus into this

210
Q

what does the filtrate from the glomerulus do?

A

collects in Bowman’s space before flowing into proximal convoluted tubule

211
Q

how is the blood in the glomerulus separated from the fluid in Bowman’s space? what does this consist of?

A

filtration barrier

single-celled capillary endothelium

BM

single-celled epithelial lining of Bowman’s capsule (podocytes)- foot processes

212
Q

how does fluid filter through the glomerular filtration barrier?

A

across endothelial cells

BM

between foot processes of podocytes

213
Q

what supplies the proximal and distal convoluted tubules?

A

peritubular capillaries

214
Q

what supplies the loop of Henle?

A

vasa recti (supplied by efferent arterioles)

215
Q

what do the peritubular capillaries and vasa recti both supply?

A

water and solutes to be secreted into the filtrate

blood to carry away water and solutes reabsorbed by the kidneys

216
Q

what is the proximal convoluted tubule?

A

longest and most coiled with simple cuboidal brush border

drains Bowmans capsule

convoluted and straight

217
Q

what is the loop of Henle?

A

sharp, hairpin like loops consisting of a descending limb coming from proximal tubule

ascending limb leading to next tubular segment

218
Q

what is the distal convoluted tubule

A

cuboidal epithelium with minimal microvilli

fluid flows from here into the collecting-duct system

219
Q

what does the collecting-duct consist of?

A

cortical collecting duct

medullary collecting duct

220
Q

what happens when the cortical/medullary collecting ducts merge?

A

urine drains into kidney’s central cavity (renal pelvis)

221
Q

what is the outer and inner portion?

A

outer - renal cortex

inner - renal medulla

222
Q

what are the types and proportions of nephron?

A

juxtamedullary (15%) and cortical (85%)

223
Q

what are the juxtamedullary nephrons? what do they do?

A

renal corpuscle lies in part of cortex closest to cortical-medullary junction

loop of Henle plunge deep into medulla and generate an osmotic gradient in medulla -> reabsorption of water

224
Q

what lies in close proximity to the juxtamedullary nephron?

A

long capillaries (vasa recta) - also loop deeply into medulla and then return to cortical-medullary junction

225
Q

what are cortical nephrons? what do they do?

A

renal corpuscles lie in the outer cortex and loop of Henle don’t penetrate deep into the medulla

some don’t have loop of Henles

involved in reabsorption and secretion but don’t contribute to the hypertonic medullary interstitium

226
Q

what does the juxtaglomerular apparatus consist of?

A

combination of macula densa and juxtaglomerular cells (granular)

227
Q

what do granular cells do?

A

secrete renin into blood, initiating RAAS

228
Q

what do macula densa cells do?

A

detect how much NaCl is passing through the distal convoluted tubule

sends signals to the granular cells to produce renin

229
Q

what is glomerular filtration? what is the SA?

A

passage of fluid from the blood into Bowman’s space to form the filtrate

SA is 1m2

230
Q

what is the flow of the glomerular filtrate?

A

glomerular capsule, proximal convoluted tubule, nephron loop, distal convoluted tubule, collecting duct, papillary duct, minor calyx, major calyx, renal pelvis, ureter, urinary bladder, urethra

231
Q

what does the male reproductive tract consist of?

A

testis, epididymis, vas deferens, prostate, seminal vesicle, penis

232
Q

what are the testis? what is their weight?

A

paired organ in the scrotum

15-19g

233
Q

what is the testis bound by? what are its layers?

A

capsule

tunica vaginalis, tunica albuginea, tunica vasculosa

234
Q

what is the tunica vaginalis (testis)?

A

projection of peritoneum

flattened layer mesothelial cells resting on BM

parietal and visceral layer

235
Q

what is the tunica albuginea (testis)?

A

thick fibrous capsule containing collagen fibres with some fibroblasts, myocytes, nerve fibres

236
Q

what is the tunica vasculosa (testis)?

A

thin innermost layer of loose connective tissue containing blood vessels and lymphatics

237
Q

where do spermatozoa form? what is their path?

A

seminephrous tubules

pass through ends of straight tubules, rete testes, efferent ducts and epididymis. from here, they leave the testis and into the vas deferens. pass into ejaculatory duct

238
Q

where does the ejaculatory duct receive secretions from?

A

seminal vesicle

239
Q

where does the urethra receive secretions from?

A

prostate

240
Q

what is the parenchyma of the testis?

A

seminiferous tubules

divided into ~250 lobules

by septa originating from the capsule

1-4 seminiferous tubules per lobule

241
Q

what do seminiferous tubules contain?

A

germ cells in varying stages of maturation

Sertoli cells - nuture germ cells

242
Q

what is the function of Sertoli cells?

A

nuture germ cells in the seminiferous tubules in the testis

243
Q

what rests on the BM of the seminiferous tubules?

A

spermatogonia

244
Q

what are the types of spermatogonia?

A

Type A - darkly stained (Ad) and pale stained (Ap)

Type B - differentiating progenitor cells with spherical nuclei and densely stained masses of chromatin

245
Q

what do Type Ad spermatogonia do?

A

stem cell population of seminiferous tubule

divide to form further type Ad and Ap cells

246
Q

what do type Ap cells do?

A

mature into type B cells

247
Q

what do spermatogonia eventually become?

A

spermatogonia -> primary spermatocyte -> secondary spermatocyte -> spermatid -> spermatozooa

248
Q

what is the histological appearance of Sertoli cells?

A

columnar cells on BM

send cytoplasmic projections around the germ cells

nuclei are irregularly shaped, folded and have a prominent nucleolus (helps distinguish from germ cells)

eosinophilic, granulated cytoplasm may have lipid vacuoles

249
Q

what are the functions of the Sertoli cells?

A

supportive, phagocytic and secretory

250
Q

structure of spermatozoa

A

head: acrosomal cap (helps penetrate egg) and nucleus
midpiece: spiral mitochondria wrapped around axoneme
tail: neck -centrioles, axoneme, plasma membrane

251
Q

what does the axoneme in a spermatozoa do? what is it?

A

responsible for sperm motility

long specialised cilium, with 9 outer doublet tubules around a single doublet pair

252
Q

what are Leydig cells? what is their function? what do they do?

A

present singly and in clusters in the interstitium between tubules

abundant cytoplasm containing lipid

Reinke’s crystalloids

may contain lipofuscin

produce testosterone

253
Q

where do Leydig cells discharge their contents into?

A

rete testes

254
Q

what is the rete testis?

A

anastomosing network of tubules at the hilum of the testis

255
Q

what is the structure of rete testis?

A

lined by simple squamous/low columnar epithelium on relatively thick BM

cilia at luminal surface

256
Q

what is the function of the rete testis?

A

mixing chamber for contents of seminiferous tubules

possible secretions

reabsorption of protein from luminal contents

257
Q

how do the rete testis discharge their content?

A

efferent ducts

258
Q

what are efferent ducts?

A

12-15 convoluted tubules which empty into the epididymis

259
Q

what is the histological appearance of efferent ducts?

A

lined by ciliated and non ciliated simple columnar epithelium with interspersed cuboidal cells (basal cells) giving a pseudostratified appearance

260
Q

what is the epididymis?

A

a tubular structure 4-5cm long containing a highly convoluted and coiled epididymal duct (5m)

261
Q

what is the histological appearance of the epididymis?

A

lined by tall columnar cells with long atypical cilia (stereocilia - non motile)

epithelium supported by thick BM surrounded by a well defined muscular coat

262
Q

what is the function of the epididymis?

A

site of absorption of testicular fluid, phagocytosis of degenerate spermatozoa, production of secretions rich in glycoproteins, syalic acid and

263
Q

where are the contents of the epididymis discharged into?

A

vas deferens

264
Q

what is the vas deferens?

A

30-40cm tubular structure arising from caudal portion of epididymis

distal part enlarged to form ampulla which joins the excretory duct of the seminal vesicle to form the ejaculatory duct

265
Q

what forms the ejaculatory duct?

A

distal part of vas deferens is enlarged to form the ampulla, which joins the excretory duct of the seminal vesicle to form the ejaculatory duct

266
Q

what is the structure of the vas deferens?

A

lined by pseudostratified columnar epithelium composed of columnar and basal cells

thick muscular wall of 3 layers of smooth muscle

267
Q

what is the prostate?

A

pear shaped glandular organ

lies at the base of the bladder

268
Q

how much does the prostate weigh?

A

up to 20g in young adult - can enlarge as you get older

269
Q

what does the prostate surround?

A

bladder neck and prostatic urethra

270
Q

what are the divisions of the prostate?

A

lobes: anterior, middle, posterior and 2 lateral lobes

peripheral, central, transitional and peri-urethral gland regions

271
Q

what happens in the clinical regions of the prostate?

A

peripheral - prostate cancer

central - enlargement with age

272
Q

what is the prostate covered by?

A

ill-defined fibro-connective tissue capsule

273
Q

what is the structure of the prostate?

A

ducts - large primary and small secondary

acini - 30-50 tubuloalveolar glands with convoluted edges

274
Q

what are prostatic acini lined by?

A

secretory cells, basal cells and neuroendocrine cells

275
Q

what are secretory cells? what do they do?

A

in the luminal side

columnar

secrete citric acid, acid phosphatases, fibrinolysin, amylase, PSA and PAP into seminal fluid

276
Q

what are the clinical uses of PSA?

A

to determine if a tissue is prostatic, detect prostate cancer

277
Q

what is PSA? what is its function?

A

prostate specific antigen

enzyme

helps liquify semen after ejaculation

278
Q

what is the stroma of the prostate?

A

smooth muscle, fibroelastic fibres, blood vessels, fibroblasts, nerves

279
Q

what is hyperplasia of the stroma and prostate gland?

A

enlarges with increasing age due to production of new cells

280
Q

what are seminal vesicles?

A

paired highly coiled tubular structures/glands posterolateral to the bladder

281
Q

where do the seminal vesicle ducts drain into?

A

ejaculatory duct

282
Q

what are seminal vesicles lined by? what is their structure?

A

lined by tall non-ciliated columnar epithelium

vacuoles and lipofuscin (within epithelial cells)

mucosa is folded

smooth muscles (2 layers) and adventitia

283
Q

how much of the ejaculate do seminal vesicle secretions comprise

A

70-80%

284
Q

what do seminal vesicle secretions consist of? what is its function?

A

fructose, prostaglandins, amino acids, proteins, citric acid and ascorbic acid (vit C)

nutrients for spermatozoa

285
Q

what does the penis consist of?

A

erectile tissue arranged into 3 components

286
Q

what is on the dorsal side of the penis?

A

left and right corpora cavernosa

287
Q

what is on the inferior side of the penis?

A

corpus spongiosum (surrounds urethra)

288
Q

what does the erectile tissue (of corpora cavernosa and spongiosa) of the penis comprise?

A

irregular vascular spaces separated by fibroelastic tissue and smooth muscle

289
Q

what are the corpora cavernosa and spongiosa surrounded by?

A

dense connective tissue - when vascular spaces engorge, it becomes erect

290
Q

nerves supply of penis

A

rich

291
Q

what are the ovaries?

A

paired organ lying on either side of the uterus close to lateral pelvis wall

292
Q

what are the attachments of the ovary?

A

to broad ligament via mesovary

to uterus by utero-ovarian ligament

to pelvic wall by suspensory ligament

293
Q

what is the ovary covered by?

A

peritoneum - single layer of modified mesothelium

poorly defined layer of fibrous connective tissue (tunica albuginea)

stroma - divided into cortex and medulla

294
Q

what is the tunica albuginea in the female reproductive tract?

A

poorly defined fibrous connective tissue layer covering the ovary - underneath the mesothelium and above the stroma

295
Q

what can the stoma in the ovary be divided into?

A

cortex and medulla with indistinct boundaries

296
Q

what does the hilum of the ovary contain?

A

where blood vessels, lymphatics and nerves enter/leave the ovary

297
Q

what does the ovarian cortex consist of?

A

spindle stromal cells arranged in whorls/storiform pattern - resemble fibroblasts

ovarian follicles

some leutinised cells

298
Q

what does the ovarian medulla consist of?

A

loose fibroelastic tissue with blood vessels, lymphatics and nerves

rete ovarii - analogue of rete testes. present at hilum

299
Q

where are follicles found in the ovary?

A

at different points, depending on stage of maturation/menstrual cycle

300
Q

what do follicles begin as?

A

primordial follicles

301
Q

where are primordial follicles located?

A

periphery of cortex

302
Q

what comprises a primordial follicle?

A

primary oocyte in resting state

surrounded by a single layer of epithelial cells (granulosa cells)

oocyte nucleus in middle

303
Q

how many primordial follicles develop in the menstrual cycle?

A

30-40

304
Q

what do primordial follicles develop into?

A

primary follicles

305
Q

what mediates the maturation of primordial follicles into primary follicles?

A

cyclic follicle stimulating hormone (FSH) secretion from anterior pituitary

306
Q

what produces FSH?

A

anterior pituitary

307
Q

what effect does FSH have on a primordial follicle?

A

oocyte enlarges

granulosa cells proliferate/enlarge - squamous to cuboidal

stromal cells become organised into connective tissue sheath

zona pellucida forms directly around oocyte

308
Q

what is the zona pellucida?

A

layer of glycoprotein between granulosa cells and oocyte

pink

309
Q

what does continued action of FSH do to the primary follicles?

A

develop into secondary follicles

granulosa cells proliferate

spaces form between granulosa cells filled with follicular fluid

cortex differentiates into theca interna and theca externa

310
Q

how is the follicular antrum formed?

A

spaces formed between granulosa cells that are filled with follicular fluid coalesce

311
Q

what are the mature follicles called? how many ovulate?

A

Graafian

~1

312
Q

what is the structure of a Graafian follicle?

A

antrum

ovum surrounded by a thick zona pellucida

layer of granulosa cells surround oocyte - corona radiata

basal lamina

theca interna and externa

cumulus ooferus

313
Q

how many primordial follicles are present at birth?

A

about 1 million

314
Q

what is atresia?

A

primordial follicles will involute and disappear

315
Q

how many primordial follicles mature to ovulate?

A

400-500 - 99% undergo atresia, 1 mature per cycle

316
Q

what is triggers ovulation?

A

lutinising hormone

317
Q

what does LH do?

A

accumulation of lipid in theca interna cells and granulosa cells

318
Q

what does leutinisation of granulosa and theca interna cells cause?

A

enlarge

lipid rich cytoplasm

319
Q

what happens to the corpus luteum if pregnancy occurs/if it doesn’t?

A

if it does, it keeps enlarging for support

if it doesn’t, it regresses

320
Q

what does the corpus luteum secrete?

A

oestrogen and progesterone

321
Q

when does regression of the corpus luteum occur if pregnancy doesn’t?

A

8-9 days after ovulation

322
Q

what characterises regression of the corpus luteum?

A

granulosa cells decrease in size, develop small densely haemotoxophilic pyknotic nuclei, and accumulation of abnormal lipid

cells undergo dissolution and are phagocytosed

progressive fibrosis by ingrowth of connective tissue (formed by ovarian stroma cells)

323
Q

what is the product of the regression of the corpus luteum?

A

formation of the corpus albicans

324
Q

what is the corpus albicans? what is its structure?

A

well circumscribed structure with convoluted borders

almost entirely composed of densely packed collagen with occasional follicles

325
Q

what eventually happens to corpus albicans?

A

resorbed/replaced by ovarian stroma

326
Q

where are the fallopian tubes?

A

run throughout length of the broad ligament

327
Q

what are the functions of the fallopian tube?

A

transports ovum to the uterus

fertilisation occurs here

328
Q

segments of the fallopian tube

A

intramural - inside uterine wall

isthmus - 2-3cm, thick walled

ampulla - expanded area

infundibulum - trumped shaped opening to peritoneum, has fimbriae

329
Q

what is the mucosa of the fallopian tube?

A

thrown into branching folds (plicae)

330
Q

what are the cell types in the fallopian tube epithelium?

A

secretory and ciliated

peg cell - effete secretory
basal - lymphocytes

331
Q

where are ciliated cells of the fallopian tube more abundant?

A

infundibular end

332
Q

where are secretory cells of the fallopian tube more abundant?

A

uterine end of tube

333
Q

what is the muscularis of the fallopian tube?

A

myosalpinx

smooth muscle:
inner circular layer
outer longitudinal layer

334
Q

what is the serosa of the fallopian tube?

A

loose fibrous connective tube covered by mesothelium

335
Q

what are the layers of the body of the uterus?

A

endometrium, myometrium and serosa

336
Q

what is the endometrium? what are its layers?

A

deep basal layer - stratum basalis

superficial functional layer - stratum compactum (towards surface) and stratum spongiosum

337
Q

what does the deep basal layer of the endometrium act as? what does it do?

A

not hormonally responsive, not lost in menstruation

acts as a reserve of stromal and endometrial epithelial cells - will be replenished

338
Q

what does the stratum spongiosum of the endometrium do?

A

undergoes changes, eventually lost in each cycle

339
Q

proliferative phase of the endometrium

A

hormonally responsive - changes according to cycle

oestrogen stimulation - causes proliferation

straight proliferating glands with mitotic activity

no luminal secretions

stromal cells are spindled and compact, mitotic activity

340
Q

when does the secretory phase of the endometrium occur?

A

after ovulation

second phase

341
Q

what influences the secretory phase of the endometrium?

A

progesterone stimulation

342
Q

what is the division of the secretory phase of the endometrium?

A

early, mid and late

343
Q

what is seen in the early secretory phase of the endometrium?

A

sub-nuclear glycogen vacuoles

344
Q

what is seen in the mid secretory phase of the endometrium?

A

vacuoles above and below the nucleus and later intraluminal secretions

glands more rounded

stroma-oedema

345
Q

what is seen in the late secretory phase of the endometrium?

A

elongated and saw-toothed glands with more intraluminal secretions

stroma - spiral arterioles, decidual change

346
Q

what is the last phase of the endometrium if pregnancy does not occur?

A

menstrual phase

347
Q

what causes the menstrual phase in the endometrium?

A

withdrawal of progesterone stimulation

348
Q

what characterises the menstrual endometrium?

A

stromal haemorrhage and granulocytes

stromal and glandular fragmentation

349
Q

what is the myometrium? what is its layers?

A

thick muscular wall of endometrium

inner longitudinal, middle circular and outer longitudinal (3 ill defined smooth muscle layers)

350
Q

what are the components of the cervix?

A

endocervix and ectocervix

351
Q

what is the endocervix composed of?

A

loose fibromuscular stroma lined by simple columnar ciliated epithelium

thrown into crypts

352
Q

what is the ectocervix composed of?

A

dense smooth muscle stroma lined by non-keratinised stratified squamous epithelium

site of squamocolumnar junction varies

353
Q

what is the ectocervix like in postmenopausal women?

A

atrophic

354
Q

what is the vagina?

A

tubular, muscular structure

355
Q

what is the mucosa of the vagina?

A

lined by non keratinising stratified squamous epithelium

fibromuscular stroma contains elastic fibres and rich vascular network

356
Q

what is the muscular wall of the vagina?

A

smooth muscle cells

inner circular
outer longitudinal

357
Q

what is the adventitia of the vagina?

A

loose connective tissue

358
Q

what often accumulates in epithelium lining vagina and ectocervix? when does it usually occur? what appearance does it give?

A

glycogen

maximal at ovulation

cytoplasm becomes clear - spongy look

359
Q

what does the vulva consist of?

A

mons pubis, labia minora and majora, vulvar vestibula, urethral meatus, Bartholins gland, clitoris, hymen, Skeon’s gland, introitus

360
Q

what is the labia majora lined by? what does it contain?

A

keratinising stratified squamous epithelium

skin adnexae

361
Q

what are the labia minora lined by?

A

mostly non keratinising stratified squamous epithelium

362
Q

what are Bartholin’s glands?

A

tubuloalveolar glands

acini lined by mucus secreting epithelium

363
Q

what are minor vestibular glands?

A

simple tubular glands lined by mucus secreting epithelium

364
Q

what are Skein’s glands? what are they lined by?

A

periurethral glands - analogous to prostate

lined by pseudostratified columnar epithelium

365
Q

what is the hymen lined by?

A

non keratinising squamous epithelium

366
Q

what is the clitoris?

A

erectile tissue rich in blood vessels and nerves

female analogue of penis

367
Q

what are common features of glands?

A

glandular epithelium

richly vascularised

secrete a variety of hormones directly into circulation

controlled by +ve and -ve feedback loops

368
Q

what is the pituitary? what are its functional components?

A

coordinates endocrine organs through feedback loops

posterior pituitary (downgrowth of hypothalamus)
anterior pituitary (epithelial structure
369
Q

what is the posterior pituitary? what is its neural tissue?

A

downward extension of the hypothalamus

axons and glial cells

370
Q

what does the posterior pituitary store/secrete?

A

oxytocin and antidiuretic hormone/vasopressin

371
Q

what is the anterior pituitary? what is its structure?

A

nested epithelial pituicytes

richly vascular fibrous stroma

several different types of pituicyte, not distinguishable on H&E

372
Q

how do we determine individual secretions of pituicytes?

A

immunohistochemistry

373
Q

what are the pituicytes of the anterior pituitary? what are their proportions?

A 
somatotrophs (50%)
lactotrophs (25%)
corticotrophs (15-20%) 
gonadotrophs (10%) 
thyrotrophs (1%)
374
Q

what do somatotrophs secrete?

A

growth hormone

375
Q

what do lactotrophs secrete?

A

prolactin

376
Q

what do corticotrophs secrete?

A

ACTH, alpha-MSH, beta-lipotrophin and beta-endorphin

377
Q

what do gonadotrops secrete?

A

FSH and LH

378
Q

what do thyrotrophs secrete?

A

thyroid stimulating hormone

379
Q

what stain is used to see nests in anterior pituitary?

A

reticulin

380
Q

where are somatotrophs found?

A

lateral wings of anterior pituitary

throughout gland

381
Q

immunohistochemical staining of somatotrophs

A

diffuse cytoplasmic positivity

growth hormone +

382
Q

what are lactotrophs?

A

polygonal cells

cytoplasmic processes wrap around other cells (hug their neighbours)

383
Q

staining of lactotrophs

A

variable prolactin staining - stains cytoplasm brown

384
Q

what are thyrotrophs?

A

angular chromophobes

elongated cytoplasmic processes (don’t hug neighbours)

385
Q

staining of thyrotrophs

A

immunohistochemical staining

cytoplasm stains brown

targets TSH

386
Q

what are gonadotrophs?

A

scattered round/oval cells

387
Q

how do gonadotrophs stain?

A

alpha subunit (common to LH and FSH)

beta LH

beta FSH

388
Q

what are corticotrophs?

A

round basophilic cells

median of gland

large cytoplasmic vacuoles

389
Q

how are pituicytes supported? how are they stained?

A

sustentacular cells, surround normal follicles

S100(protein) +ve - stains them brown

390
Q

what are benign tumors of the pituitary gland?

A

pituitary adenoma

391
Q

what happens as the pituitary adenoma expands?

A

expands out of sella tursica

becomes pituitary adenoma macro - presses on optic chiasm

392
Q

what is the HandE staining of an adenoma?

A

rosettes with capillary in the middle

393
Q

changes in reticulin in an adenoma

A

nests become expanded in hyperplasia, in adenomas the normal architecture has been lost and reticulin only surrounds the blood vessels

394
Q

where is the pineal gland located?

A

just below posterior end of the corpus callosum. covered by meninges

395
Q

what is the equation for pH?

A

-log1{H+}

396
Q

what is the normal range of pH for blood?

A

7.35-7.45

397
Q

acid vs base

A

acid - donates H+ ions

base - accepts H+ ions

398
Q

what is acidosis/alkalosis?

A

acidosis: blood more acid than normal
alkalosis: blood more alkaline than normal

399
Q

what is acidemia/alkalemia?

A

low blood pH

high blood pH

400
Q

what is an anion gap?

A

difference between measured anions (negative and cations (positive)

[Na+] + [K+] - [Cl-] - [HCO3-]

401
Q

what is the normal anion gap?

A

10-16

402
Q

what is a wide anion gap caused by?

A

lactic acidosis, ketoacidosis, ingestion of acid, renal failure

403
Q

what is a narrow anion gap caused by?

A

GI HCO3- loss, renal tubular acidosis

404
Q

what are types of urinary phosphate buffers?

A

urinary phosphate buffer and ammonium urinary buffer

both in proximal tubule

405
Q

what is the urinary phosphate buffer?

A

alkaline phosphate (HPO4 2-) - most common urinary buffer

acts in proximal tubule

406
Q

what does alkaline phosphate (HPO4 2-) do? what happens to it?

A

when all of filtered HCO3- has combined with secreted H+, the additional H+ secreted starts combining with filtered non bicarbonate buffers

H+ (from dissociation of H2CO3) combines with HPO4 2- to form H2PO4-, which is excreted in the urine

407
Q

what happens with the HCO3- with the phosphate buffer?

A

enters the interstitial fluid - no absorption from tubular lumen

net gain of HCO3- in interstitium and blood plasma -> alkalinises it

408
Q

when do significant amounts of H+ combine with filtered non bicarbonate buffers?

A

only after the filtered HCO3- has all been reabsorbed

409
Q

formation of ammonia and bicarbonate in the proximal tubule

A

proximal tubular epithelial cells take up glutamine from glomerular filtrate and peritubular plasma and metabolise it to form NH3 (ammonia) and HCO3- (bicarbonate)

410
Q

how is glutamine transferred into the tubular epithelial cell?

A

with Na+

411
Q

what is the fate of the NH3 formed from glutamine in the tubular epithelial cell?

A

reacts with H+ in the cell (either derived from dissociation of H2CO3 or that absorbed due to Na+ reabsorption) to form NH4+ (ammonium ion)

412
Q

what is the fate of the ammonium ion formed from NH3?

A

actively secreted via Na+/NH4+ countertransport into the lumen and excreted

413
Q

what is the fate of the HCO3- formed from glutamine in the tubular epithelial cell?

A

moves into peritubular capillaries and increases HCO3- levels (net gain of HCO3-) -> alkalinising blood plasma

414
Q

what is respiratory acidosis?

A

failure to get rid of CO2 resulting in a decrease in pH as CO2 builds up

415
Q

what are the causes of respiratory acidosis?

A

hyperventilation
COPD
any cause of respiratory failure (pulmonary embolism: type 1, hypoventilation: type 2)

416
Q

what is the renal compensation for respiratory acidosis? how long will it take?

A

the kidneys will increases H+ secretion in form of NH4+ and release more HCO3- into the plasma which increases pH, via the ammonium buffer

will take days

417
Q

what is respiratory alkalosis?

A

too much CO2 lost resulting in an increased pH

418
Q

what are the causes of respiratory alkalosis?

A

CO2 depletion due to hyperventilation
hypoxia
type 1 respiratory failure: pulmonary embolism (decrease in O2 and decrease/no change in CO2)

419
Q

what is the renal compensation for respiratory alkalosis?

A

kidneys decrease H+ secretion - retain it and help it return to normal

decreased H+ secretion -> decrease in HCO3- reabsorption (more excretion) - increases pH

420
Q

what is metabolic acidosis?

A

excess acid production (intercalated cells release acid) leading to a decrease in pH

421
Q

what are the causes of metabolic acidosis?

A

renal failure
GI HCO3- loss
dilution of blood - the more H20 in blood, the more acidic it gets
failure of H+ excretion (hypoaldosteroneism)
excess H+ (ketoacidosis)

422
Q

what effect does diluting blood have on acidity?

A

more H2O in blood, the more acidic it gets

423
Q

what is hypoaldosteroneism?

A

insufficient aldosterone is released so less Na+ reabsorbed and less H+ secreted (Na+/H+ countertransporter)

424
Q

what is the respiratory compensation for metabolic acidosis?

A

decrease in pH stimulates chemoreceptors of the lung -> enhanced respiration -> fall in CO2 -> increase in pH

425
Q

what is metabolic alkalosis?

A

pH of a tissue is elevated above 7.45

426
Q

what are the causes of metabolic alkalosis?

A

increase in pH

vomiting, volume depletion alkali ingestion, hyperaldosteronism, hyperkalaemia (increased aldosterone release)

427
Q

how does hyperkalaemia affect aldosterone release?

A

increases it

428
Q

what is the respiratory compensation of metabolic alkalosis?

A

increase in pH inhibits chemoreceptors -> reduced respiration -> increased CO2 -> decreased pH

429
Q

where is EPO produced?

A

kidney - in peritubular cells in interstitial space of renal cortex

430
Q

what does EPO do?

A

stimulates bone marrow maturation of erythrocytes

431
Q

what increases EPO?

A

anaemia, altitude and cardiopulmonary disorders

432
Q

what decreases EPO?

A

polycythaemia (abnormally increased Hb in blood), renal failure

433
Q

what is the first step in vitamin D metabolism?

A

absorbed in skin from solar UVB light as 7-dehydrocholesterol, converted into D3 (cholecalciferol)

434
Q

what is vitamin D3?

A

cholecalciferol

435
Q

what does the liver do in vitamin D metabolism?

A

converts cholecalciferol into calcidiol (25 hydroxy vitamin D) via vitamin D3 -25- hydroxylase

436
Q

what is calcidol?

A

25-hydroxy-vitamin D

437
Q

where is vitamin D obtained from?

A

skin as 7-dehydrocholesterol

dietary intake as vitamin D3 (cholecalciferol): oily fish, meat, eggs, fortified foods

438
Q

what does the kidney do in vitamin D metabolism?

A

converts calcidol (25-hydroxy-vitamin D) to calcitriol (1,25-dihydroxy-vitamin D) via 25(OH)D3-1-alpha-hydroxylase

439
Q

what are the effects of calcitriol?

A

intestine: increases Ca3(PO4)2 absorption
bone: inhibits bone resorption
kidney: increases Ca3(PO4)2 reabsorption
parathyroid: inhibits parathyroid hormone

440
Q

where are the adrenals located?

A

above kidneys - retroperitoneal

441
Q

what is the arterial supply of the adrenals?

A

superior adrenal artery - from inferior phrenic

middle adrenal artery - from abdominal aorta

inferior adrenal artery - from renal artery

442
Q

what is the venous drainage of the adrenals?

A

right adrenal vein drains directly into the IVC

left adrenal vein drains into the left renal vein

443
Q

what is the nerve supply of the adrenals?

A

splanchnic nerves

444
Q

what is the structure of the adrenals?

A

cortex and medulla

445
Q

what are the hormones secreted by the adrenal cortex?

A 
aldosterone
cortisol
corticosterone
dehydroepiandrosterone (DHEA)
androstenedione
446
Q

what is the adrenal cortex divided into?

A

from outside in:

zona glomerulosa - mineralocorticoids e.g. aldosterone

zona fasiculata - glucocorticoids e.g. cortisol and small amounts of androgens

zona reticularis - androgens (sex hormones) and small amounts of cortisol

GFR - Makes Good Sex

447
Q

what is important for glucocorticoids and mineralocorticoids?

A

negative feedback

448
Q

what controls the adrenal medulla?

A

sympathetic control

449
Q

what does the adrenal medulla secrete?

A

2 hormones belonging to catecholamine family - adrenaline and noradrenaline, which cause cortex to secrete further hormones

450
Q

what does the adrenal medulla respond to? how?

A

stress - dilates pupils, increases glycogenolysis, increases lipolysis, increases sweating, increases heart rate and inhibits insulin release

451
Q

what is the precursor to all corticosteroids?

A

cholesterol

452
Q

what are corticosteroids?

A

lipid soluble - can pass through biological membranes

bind to specific intracellular receptors

alter gene expression directly or indirectly

exact action depends on structure

453
Q

what does the zona glomerulosa secrete?

A

mineralocorticoids

454
Q

what is the role of mineralocorticoids? give an example?

A

secreted by zona glomerulosa of the adrenal gland

regulates body electrolytes

aldosterone (due to aldosterone synthase)

455
Q

what does aldosterone do? how is it released?

A

maintains salt balance and BP

triggered by release of renin by juxtaglomerular cells in afferent arterioles of kidney - problems with kidney affect release

456
Q

what does the zona fasiculata release?

A

glucocorticoids e.g. cortisol and corticosterone

457
Q

what does cortisol do?

A

affects metabolism of glucose - actions on most tissues

facilitates bodies response to stress and regulation of immune system

458
Q

where is cortisol synthesised?

A

zona fasiculata and zona reticularis

459
Q

what is stress?

A

real/perceived threat to homeostasis - any change in temperature, water intake or other factors are designed to prevent a significant change in a variable

460
Q

what are examples of threat that cause stress?

A

physical trauma, prolonged exposure to cold, prolonged heavy exercise, infection, shock, decreased oxygen supply, sleep deprivation, pain, emotional stress

461
Q

what does threat trigger?

A

increase in cortisol

462
Q

what also increases in response to stress?

A

sympathetic nervous system activity and the release of hormone adrenaline from the adrenal medulla increases

463
Q

what is the process of stress and its effects?

A

stress detected and transmitted neutrally to the hypothalamus

stimulates secretion of corticotropin-releasing hormone (CRH) from hypothalamus

hormone carried by hypothalamic-hypophyseal portal vessels to anterior pituitary - stimulates release of adrenocorticotropic hormone (ACTH)

ACTH circulates through blood and travels to adrenal cortex, stimulates cortisol release

464
Q

where is stress transmitted to?

A

hypothalamus

465
Q

what does stress stimulate in the hypothalamus?

A

secretion of corticotropin-releasing hormone (CRH)

466
Q

what does CRH do?

A

released from hypothalamus - corticotropin-releasing hormone (CRH)

carried by hypothalamic-hypophyseal portal vessels to anterior pituitary - stimulates release of ACTH

467
Q

what does ACTH do?

A

released by anterior pituitary - adrenocorticotropic hormone

travels to adrenal cortex and stimulates cortisol release

468
Q

what is secretion of ACTH stimulated by?

A

CRH from hypothalamus

(lesser extent) vasopressin - increases in response to stress

469
Q

forms of cortisol in circulation

A

90% bound to corticosteroid-binding globulin (CBG)

5% bound to albumin

5% free

only free cortisol is bioavailable

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